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407 records returned

Regulation of macrophage motility by Irgm1.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
IRG are a family of IFN-regulated proteins that are critical for resistance to infection. Mouse IRG proteins are divided into GMS and GKS subfamilies, based on a sequence within the G1 GTP-binding motif. The GMS proteins have a particularly profound impact on immunity, as typified by Irgm1, of which absence leads to a complete loss of resistance to a variety of intracellular bacteria and protozoa. The underlying molecular and cellular mechanisms are not clear. Here, we use time-lapse microscopy and cell-tracking analysis to demonstrate that Irgm1 is required for motility of IFN-gamma-activated macrophages. The absence ...
Source: Journal of Leukocyte Biology - November 17, 2009 Category: Hematology Authors: Henry SC, Traver M, Daniell X, Indaram M, Oliver T, Taylor GA Tags: J Leukoc Biol Source Type: journals

The battlefield of perforin/granzyme cell death pathways.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
A pore-forming protein, PRF, and serine proteases, Grz, are key effector molecules of CL. These toxins are stored within secretory granules, which exocytose their contents in response to immune synapse formation between the CL and virus-infected or transformed target cell. There, PRF and Grz synergize to induce various apoptotic death pathways and to maintain immune homeostasis. Mechanistic aspects of the synergy and apoptotic mechanisms are still not fully understood, and the current review will address some of the hotly debated controversies in the field. PMID: 19915166 [PubMed - as supplied by publisher] (Source...
Source: Journal of Leukocyte Biology - November 13, 2009 Category: Hematology Authors: Hoves S, Trapani JA, Voskoboinik I Tags: J Leukoc Biol Source Type: journals

Modulated selection of IGHV gene somatic hypermutation during systemic maturation of human plasma cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, human PCs were isolated from tonsil, blood, and BM, their IGHV3 and IGHV6 genes were sequenced, and their SHM were evaluated. The SHM analysis reveals the existence of a maturational gradient in these genes, as demonstrated by a progressive increase in the frequency of total and R mutations and total and NC aa changes following the direction: tonsil --> blood --> BM. The ratio of R to S mutations in the CDR1 and -2, but not in the FRs, increases from tonsil to blood and BM; this parameter reaches a maximum threshold when more than 10 mutations/sequence occur. Further analyses indicate that CDR1 and CDR...
Source: Journal of Leukocyte Biology - November 13, 2009 Category: Hematology Authors: Jiménez-Gómez G, Gómez-Perales J, Ramos-Amaya A, González-García I, Campos-Caro A, Brieva JA Tags: J Leukoc Biol Source Type: journals

Mesenchymal stem cells respond to TNF but do not produce TNF.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Previously, we demonstrated that several TLRs are expressed on cord blood-derived USSC. Stimulation of USSC with TLR agonists resulted in a marked increase of IL-6 and IL-8 production. Interestingly, TNF was undetectable after TLR stimulation, which appeared to be a result of an inactivated TNF promoter in USSC. Here, we elaborate this study by demonstrating that although USSC do not produce TNF, they are susceptible to TNF stimulation, resulting in NF-kappaB translocation and cytokine production. Additionally, we compared different stem cell sources for their ability to produce TNF. Interestingly, we found that the TN...
Source: Journal of Leukocyte Biology - November 6, 2009 Category: Hematology Authors: van den Berk LC, Jansen BJ, Siebers-Vermeulen KG, Roelofs H, Figdor CG, Adema GJ, Torensma R Tags: J Leukoc Biol Source Type: journals

Opposite effects of simvastatin on the bactericidal and inflammatory response of macrophages to opsonized S. aureus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Besides lowering circulating cholesterol, statins act as immunomodulators. Although the effects of statins on lymphocyte activation and differentiation have been clearly defined, there is no consensus as to effects of these drugs on phagocytes. We have addressed the outcome of simvastatin treatment on the activation and effector function of human macrophages in the pathophysiologically relevant context of challenge with an opportunistic pathogen. We provide evidence that: simvastatin blocks the biological effects rapidly triggered by IgG-opsonized bacteria (phagocytosis and oxidative burst) while enhancing the delayed ...
Source: Journal of Leukocyte Biology - November 5, 2009 Category: Hematology Authors: Benati D, Ferro M, Savino MT, Ulivieri C, Schiavo E, Nuccitelli A, Pasini FL, Baldari CT Tags: J Leukoc Biol Source Type: journals

Induction of HIF-1{alpha} and the glycolytic pathway alters apoptotic and differentiation profiles of activated human T cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The majority of in vitro studies involving lymphocytes is performed in AtmO2, and the PhysO2 that T cells encounter are variable but commonly much lower. Previous studies showed changed kinetics and delayed proliferation of human T cells at PhysO2. Here, we show that CD3/CD28-dependent T cell activation induces faster cell cycling at AtmO2 than at PhysO2 (here taken to be 2%). Concomitantly with HIF-1alpha expression, we observed a switch in the T cell respiratory pathway toward glycolysis at PhysO2. Thus, modulating available glucose levels showed that at PhysO2, T cells rely more on glycolysis, associated with a high...
Source: Journal of Leukocyte Biology - November 5, 2009 Category: Hematology Authors: Larbi A, Zelba H, Goldeck D, Pawelec G Tags: J Leukoc Biol Source Type: journals

Activation-induced accumulation of B and T lymphocyte attenuator at the immunological synapse in CD4+ T cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
BTLA, a recently cloned coreceptor expressed on lymphocytes, negatively regulates cell activation by recruiting SHP-1/SHP-2. However, the mechanisms that regulate the intracellular localization of BTLA and its trafficking to the cell surface in T cells are still unknown. To determine the mechanisms that regulate the expression of BTLA on the surface of T cells, we examined the subcellular localization of BTLA in mouse T cells in a steady state, as well as upon activation by using a confocal laser-scanning microscopy. We found that BTLA was localized mainly in the Golgi apparatus and secretory lysosomes in resting CD4(+...
Source: Journal of Leukocyte Biology - November 5, 2009 Category: Hematology Authors: Owada T, Watanabe N, Oki M, Oya Y, Saito Y, Saito T, Iwamoto I, Murphy TL, Murphy KM, Nakajima H Tags: J Leukoc Biol Source Type: journals

Biogenesis of secretory organelles during B cell differentiation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, the Golgi remains consistently as a single juxtanuclear structure but linearly expands sixfold in volume during B cell activation. Furthermore, following active cell proliferation, ER exit sites proliferate rapidly, increasing almost fourfold in number, in parallel with a sharp increase in Ig secretion. These findings demonstrate that the control of organelle biogenesis and expansion in primary human B cells are differentially regulated by cargo flux caused by Ig synthesis. PMID: 19889725 [PubMed - as supplied by publisher] (Source: Journal of Leukocyte Biology)
Source: Journal of Leukocyte Biology - November 4, 2009 Category: Hematology Authors: Kirk SJ, Cliff JM, Thomas JA, Ward TH Tags: J Leukoc Biol Source Type: journals

Phagosomal retention of Francisella tularensis results in TIRAP/Mal-independent TLR2 signaling.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We reported previously that Ft LVS elicited strong, dose-dependent NF-kappaB reporter activity in TLR2-expressing human embryo kidney 293 T cells and that Ft LVS-induced murine macrophage proinflammatory cytokine gene and protein expression is TLR2-dependent. We demonstrated further that Ft can signal through TLR2 from within the phagosome and that phagosomal retention of Ft leads to greatly increased expression of a subset of proinflammatory genes. The two adaptor proteins associated with TLR2-mediated signaling are MyD88 and TIRAP. Although MyD88 is absolutely required for the Ft-induced macrophage cytokine response, the...
Source: Journal of Leukocyte Biology - November 4, 2009 Category: Hematology Authors: Cole LE, Laird MH, Seekatz A, Santiago A, Jiang Z, Barry E, Shirey KA, Fitzgerald KA, Vogel SN Tags: J Leukoc Biol Source Type: journals

The adaptor protein p66shc is a positive regulator in the angiogenic response induced by hypoxic T cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In conclusion, hypoxic T cells may contribute to the onset of angiogenesis through a novel VEGF-mediated mechanism, where p66Shc acts as a positive regulator. PMID: 19889727 [PubMed - as supplied by publisher] (Source: Journal of Leukocyte Biology)
Source: Journal of Leukocyte Biology - November 4, 2009 Category: Hematology Authors: Naldini A, Morena E, Pucci A, Pellegrini M, Baldari CT, Pelicci PG, Presta M, Ribatti D, Carraro F Tags: J Leukoc Biol Source Type: journals

Adenosine A2A receptor activation limits graft-versus-host disease after allogenic hematopoietic stem cell transplantation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
GVHD is a major barrier to broader use of allogenic HSCT for nonmalignancy clinical applications such as the treatment of primary immunodeficiencies and hemoglobinopathies. We show in a murine model of C57BL/6J (H2-k(b)) --> B6D2F1/J (H2-k(b/d)) acute GVHD that when initiated 2 days before transplant, the activation of the adenosine A2AR with the selective agonist ATL146e inhibits the weight loss and mortality associated with disease progression. Furthermore, circulating levels of proinflammatory cytokines and chemokines, including IFN-gamma, IL-6, CCL2, KC, and G-CSF, are reduced significantly by 14-day ATL146e tre...
Source: Journal of Leukocyte Biology - November 4, 2009 Category: Hematology Authors: Lappas CM, Liu PC, Linden J, Kang EM, Malech HL Tags: J Leukoc Biol Source Type: journals

Syk expression in peripheral blood leukocytes, CD34+ progenitors, and CD34-derived basophils.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In human basophils from different subjects, maximum IgE-mediated histamine release and the level of syk protein expression correlate well. It is not clear when in the basophil's lifetime the set-point for syk expression is reached or how expression levels are determined for a given individual. An examination of syk expression in peripheral blood eosinophils, neutrophils, monocytes, B and T cells, DCs, and NK cells showed that with the exception of T cells, basophils were unique in expressing low levels of syk. No correlations were observed between syk expression in basophils and other types of leukocytes, suggesting a ...
Source: Journal of Leukocyte Biology - November 4, 2009 Category: Hematology Authors: Ishmael SS, Macglashan Jr DW Tags: J Leukoc Biol Source Type: journals

ICOS promotes IL-17 synthesis in colonic intraepithelial lymphocytes in IL-10-/- mice.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In the absence of IL-10, colonic inflammation ensues, which is characterized by high levels of IL-17. Here, we demonstrate a direct correlation between ICOS expression and IL-17 production in cIELs. IL-10(-/-) mice had increased numbers of cIELs and greater colon weight. Although the CD69 early activation antigen was expressed on cIELs from normal and IL-10(-/-) mice, ICOS was expressed only on cIELs from IL-10(-/-) mice. IL-17-producing cells in IL-10(-/-) mice consisted of CD4(+) and CD8(+) cIELs; however, CD4(+) cells were the predominant IL-17-producing cell population. Culture of cIELs from IL-10(-/-) mice with IL...
Source: Journal of Leukocyte Biology - November 4, 2009 Category: Hematology Authors: Schaefer JS, Montufar-Solis D, Vigneswaran N, Klein JR Tags: J Leukoc Biol Source Type: journals

Immune system dysregulation during spaceflight: clinical risk for exploration-class missions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19875627 [PubMed - in process] (Source: Journal of Leukocyte Biology)
Source: Journal of Leukocyte Biology - October 31, 2009 Category: Hematology Authors: Crucian B, Sams C Tags: J Leukoc Biol Source Type: journals

Liver X receptor alpha (LXRalpha) as a therapeutic target in chronic lymphocytic leukemia (CLL).Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19875628 [PubMed - in process] (Source: Journal of Leukocyte Biology)
Source: Journal of Leukocyte Biology - October 31, 2009 Category: Hematology Authors: Christopherson KW, Landay A Tags: J Leukoc Biol Source Type: journals

PSGL-1--the hidden player in T cell trafficking into the brain in multiple sclerosis?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19875629 [PubMed - in process] (Source: Journal of Leukocyte Biology)
Source: Journal of Leukocyte Biology - October 31, 2009 Category: Hematology Authors: Engelhardt B Tags: J Leukoc Biol Source Type: journals

When two is better than one: macrophages and neutrophils work in concert in innate immunity as complementary and cooperative partners of a myeloid phagocyte system.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The antimicrobial effector activity of phagocytes is crucial in the host innate defense against infection, and the classic view is that the phagocytes operating against intracellular and extracellular microbial pathogens are, respectively, macrophages and neutrophils. As a result of the common origin of the two phagocytes, they share several functionalities, including avid phagocytosis, similar kinetic behavior under inflammatory/infectious conditions, and antimicrobial and immunomodulatory activities. However, consequent to specialization during their differentiation, macrophages and neutrophils acquire distinctive, c...
Source: Journal of Leukocyte Biology - October 22, 2009 Category: Hematology Authors: Silva MT Tags: J Leukoc Biol Source Type: journals

Pivotal Advance: Pharmacological manipulation of inflammation resolution during spontaneously resolving tissue neutrophilia in the zebrafish.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Zebrafish are a unique model for pharmacological manipulation of physiological processes such as inflammation; they are small and permeable to many small molecular compounds, and being transparent, they permit the visualization and quantitation of the inflammatory response by observation of transgenically labeled inflammatory cell populations. Using a transgenic line specifically labeling neutrophils in vivo (mpx:GFP), we studied the effects of a range of pharmacological agents on the resolution of inflammation in vivo. These agents were selected for their ability to modulate neutrophil function and lifespan in human n...
Source: Journal of Leukocyte Biology - October 22, 2009 Category: Hematology Authors: Loynes CA, Martin JS, Robertson A, Trushell DM, Ingham PW, Whyte MK, Renshaw SA Tags: J Leukoc Biol Source Type: journals

The phenotype of murine wound macrophages.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study characterized wound macrophage phenotype in the PVA sponge wound model in mice. Eighty-five percent of wound macrophages isolated 1 day after injury expressed Gr-1, but only 20% of those isolated at 7 days expressed this antigen. Macrophages from 1-, 3-, and 7-day wounds expressed markers of alternative activation, including mannose receptor, dectin-1, arginase 1, and Ym1, but did not contain iNOS. Day 1 wound macrophages produced more TNF-alpha, more IL-6, and less TGF-beta than Day 7 wound macrophages. Wound macrophages did not produce IL-10. The cytokines considered necessary for alternative activation of mac...
Source: Journal of Leukocyte Biology - October 22, 2009 Category: Hematology Authors: Daley JM, Brancato SK, Thomay AA, Reichner JS, Albina JE Tags: J Leukoc Biol Source Type: journals

Reduced transcript stabilization restricts TNF-{alpha} expression in RAW264.7 macrophages infected with pathogenic mycobacteria: evidence for an involvement of lipomannan.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Despite the critical role that TNF-alpha plays in the containment of mycobacterial infection, the mechanisms involved in regulation of its expression by mycobacteria are poorly defined. We addressed this question by studying MAP, which causes a chronic enteritis in ruminants and is linked to human Crohn's disease. We found that in MAP-infected macrophages, TNF-alpha gene expression was substantially lower than in macrophages infected with nonpathogenic MS or stimulated with LPS. TNF-alpha transcription alone could not fully explain the differential TNF-alpha mRNA expression, suggesting that there must be a substantial ...
Source: Journal of Leukocyte Biology - October 22, 2009 Category: Hematology Authors: Basler T, Holtmann H, Abel J, Eckstein T, Bäumer W, Valentin-Weigand P, Goethe R Tags: J Leukoc Biol Source Type: journals

Pivotal Advance: Glycyrrhizin restores the impaired production of {beta}-defensins in tissues surrounding the burn area and improves the resistance of burn mice to Pseudomonas aeruginosa wound infection.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The decreased production of antimicrobial peptides in tissues surrounding the burn sites has been described in patients with severe burn injury. Small numbers of Pseudomonas aeruginosa spread easily to the whole body of burn mice when infected at burn site tissues. Gr-1(+)CD11b(+) cells, demonstrated in tissues surrounding the burn site, are inhibitory on the production of antimicrobial peptides by EK. In this paper, the decreased production of antimicrobial peptides by EK influenced by Gr-1(+)CD11b(+) cells was shown to be restored by glycyrrhizin. CCL2 and IL-10 were determined to be effector soluble factors for the ...
Source: Journal of Leukocyte Biology - October 19, 2009 Category: Hematology Authors: Yoshida T, Yoshida S, Kobayashi M, Herndon DN, Suzuki F Tags: J Leukoc Biol Source Type: journals

Signaling through TLR7 enhances the immunosuppressive activity of murine CD4+CD25+ T regulatory cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we show that mouse CD4(+)CD25(+) Treg cells express TLR7 mRNA and protein. We therefore used the TLR7 agonists imiquimod, gardiquimod, and single-stranded poly(U) to show that TLR7 stimulation enhanced the ability of murine Treg cells to suppress anti-CD3/anti-CD28 mAb-coated bead-stimulated proliferation of syngeneic CD4(+)CD25(-) Tresp cells. In contrast, imiquimod failed to enhance the suppressor function of Treg cells from mice deficient in the MyD88 adaptor protein involved in TLR7 and other TLR signal transduction. Imiquimod increased murine Treg cell-mediated suppression of Tresp cell proliferation in...
Source: Journal of Leukocyte Biology - October 19, 2009 Category: Hematology Authors: Forward NA, Furlong SJ, Yang Y, Lin TJ, Hoskin DW Tags: J Leukoc Biol Source Type: journals

Immunopathogenesis of polymicrobial otitis media.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
OM, or inflammation of the middle ear, is a highly prevalent infection in children worldwide. OM is a multifactorial disease with multiple risk factors, including preceding or concurrent viral URT infection. Hence, OM is also a polymicrobial disease. The mechanisms by which viruses predispose to bacterial OM are replete; however, all are predicated on the general principle of compromise of primary host airway defenses. Thus, despite an as-yet incomplete understanding of the molecular mechanisms involved in bacterial superinfection of a virus-compromised respiratory tract, the URT viruses are known to induce histopathol...
Source: Journal of Leukocyte Biology - October 19, 2009 Category: Hematology Authors: Bakaletz LO Tags: J Leukoc Biol Source Type: journals

Antagonistic roles of four SR proteins in the biosynthesis of alternatively spliced tissue factor transcripts in monocytic cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this report, we show for the first time that two other SR proteins expressed in human monocytes, SRp40 and SC35, antagonize ASF/SF2 and SRp55 by competing for binding to certain sites in exon 5, thereby promoting TF exon 5 exclusion, an event unique to asTF biosynthesis. We also show that the intron preceding TF exon 5 possesses characteristics rarely found in U2 introns. Our findings indicate that modulation of TF pre-mRNA splicing can be accomplished via modification of SR proteins' activity, facilitating development of novel therapeutic strategies to modulate the "TF profile" of monocytes/macrophages. PMID: 19843...
Source: Journal of Leukocyte Biology - October 19, 2009 Category: Hematology Authors: Chandradas S, Deikus G, Tardos JG, Bogdanov VY Tags: J Leukoc Biol Source Type: journals

Decreased ERK and JNK signaling contribute to gene overexpression in "senescent" CD4+CD28- T cells through epigenetic mechanisms.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report that signaling through the ERK and JNK pathways is decreased in CD4+CD28- relative to CD4+CD28+ cells from the same individuals and that ERK and JNK pathway inhibition decreases Dnmt1 and -3a levels, which in turn, causes demethylation and overexpression of the TNFSF7 (CD70) gene. We also report that CD4+CD28- T cells overexpress PP5, a stress-induced inhibitor of the ERK and JNK signaling pathways that may contribute to the signaling defects. We conclude that decreased ERK and JNK signaling in the CD4+CD28- subset, arising with replicative stress, can lead to the overexpression of normally suppressed genes throu...
Source: Journal of Leukocyte Biology - October 19, 2009 Category: Hematology Authors: Chen Y, Gorelik GJ, Strickland FM, Richardson BC Tags: J Leukoc Biol Source Type: journals

Antigen-induced Erk1/2 activation regulates Ets-1-mediated sensitization of CD8+ T cells for IL-12 responses.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The presence of IL-12 during antigen stimulation instructs naive CD8+ T cells for long-term effector responses, but their mechanisms of collaboration are not understood completely. Herein, we report that CD8+ T cells (OT-I T cells) stimulated with antigen for a longer duration show enhanced sensitization to IL-12 as a result of Erk1/2-dependent, increased Ets-1 phosphorylation and subsequent increases in IL-12Rbeta2 expression. Correspondingly, naive OT-I T cells stimulated by antigen for a longer duration in the presence of IL-12, irrespective of frequency of APCs, show robust effector maturation and mount long-term a...
Source: Journal of Leukocyte Biology - October 19, 2009 Category: Hematology Authors: Li Q, Eppolito C, Odunsi K, Shrikant PA Tags: J Leukoc Biol Source Type: journals

Monocyte heterogeneity underlying phenotypic changes in monocytes according to SIV disease stage.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Infection by HIV is associated with the expansion of monocytes expressing CD16 antigens, but the significance of this in HIV pathogenesis is largely unknown. In rhesus macaques, at least three subpopulations of blood monocytes were identified based on their expression of CD14 and CD16: CD14(high)CD16(-), CD14(high)CD16(low), and CD14(low)CD16(high). The phenotypes and functions of these subpopulations, including CD16(+) monocytes, were investigated in normal, uninfected rhesus macaques and macaques that were infected with SIV or chimeric SHIV. To assess whether these different monocyte subpopulations expand or contract...
Source: Journal of Leukocyte Biology - October 19, 2009 Category: Hematology Authors: Kim WK, Sun Y, Do H, Autissier P, Halpern EF, Piatak M, Lifson JD, Burdo TH, McGrath MS, Williams K Tags: J Leukoc Biol Source Type: journals

Human defensins and LL-37 in mucosal immunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Defensins are widespread in nature and have activity against a broad range of pathogens. Defensins have direct antimicrobial effects and also modulate innate and adaptive immune responses. We consider the role of human defensins and the cathelicidin LL-37 in defense of respiratory, gastrointestinal, and genitourinary tracts and the oral cavity, skin, and eye. Human beta-defensins (hBD) and human defensins 5 and 6 (HD5 and -6) are involved most obviously in mucosal responses, as they are produced principally by epithelial cells. Human alpha-defensins 1-4 (or HNPs 1-4) are produced principally by neutrophils recruited to...
Source: Journal of Leukocyte Biology - October 5, 2009 Category: Hematology Authors: Doss M, White MR, Tecle T, Hartshorn KL Tags: J Leukoc Biol Source Type: journals

Interleukin 27: a double-edged sword for offense and defense.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cytokine-mediated immunity plays a crucial role in the pathogenesis of various diseases including infection and autoimmune diseases. IL-27, along with IL-12, -23, and -35, belongs to the IL-12 cytokine family. These family members play roles in regulation of Th cell differentiation. IL-27 is unique in that although it induces Th1 differentiation, the same cytokine suppresses immune responses. In the absence of IL-27-mediated immunosuppression, hyperproduction of various proinflammatory cytokines concomitant with severe inflammation is observed. The immunosuppressive effects of IL-27 depend on IL-2 suppression, inhibiti...
Source: Journal of Leukocyte Biology - October 1, 2009 Category: Hematology Authors: Yoshida H, Nakaya M, Miyazaki Y Tags: J Leukoc Biol Source Type: journals

MMP-8 promotes polymorphonuclear cell migration through collagen barriers in obliterative bronchiolitis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Increased levels of MMP-8 (neutrophil collagenase) have been reported in OB, but the biological role of MMP-8 in OB is not known. MMP-8 is an interstitial collagenase highly expressed by polymorphonuclear leukocytes, which are prominent in early OB. Here, we show that MMP-8 promotes migration of PMNs through the collagen-rich matrix in a mouse heterotopic airway transplant model of OB. Overall, MMP-8(-/-) mice had significantly fewer PMNs in the airway lumen 2 and 14 days post-transplantation, and the percentage of PMNs traversing the matrix to the lumen was decreased markedly in the MMP-8(-/-) compared with WT mice at...
Source: Journal of Leukocyte Biology - October 1, 2009 Category: Hematology Authors: Khatwa UA, Kleibrink BE, Shapiro SD, Subramaniam M Tags: J Leukoc Biol Source Type: journals

HIV-1 regulation of latency in the monocyte-macrophage lineage and in CD4+ T lymphocytes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The introduction in 1996 of the HAART raised hopes for the eradication of HIV-1. Unfortunately, the discovery of latent HIV-1 reservoirs in CD4+ T cells and in the monocyte-macrophage lineage proved the optimism to be premature. The long-lived HIV-1 reservoirs constitute a major obstacle to the eradication of HIV-1. In this review, we focus on the establishment and maintenance of HIV-1 latency in the two major targets for HIV-1: the CD4+ T cells and the monocyte-macrophage lineage. Understanding the cell-type molecular mechanisms of establishment, maintenance, and reactivation of HIV-1 latency in these reservoirs is cr...
Source: Journal of Leukocyte Biology - October 1, 2009 Category: Hematology Authors: Redel L, Le Douce V, Cherrier T, Marban C, Janossy A, Aunis D, Van Lint C, Rohr O, Schwartz C Tags: J Leukoc Biol Source Type: journals

Regulation of TNF-induced oxygen radical production in human neutrophils: role of {delta}-PKC.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we demonstrate that inhibition of delta-PKC with a dominant-negative delta-PKC TAT peptide resulted in a significant delay in the onset time of TNF-elicited O2(-) generation but had no effect on Vmax, indicating an involvement of delta-PKC in the initiation of O2(-) production. In contrast, fMLP-elicited O2(-) production in adherent and nonadherent neutrophils was delta-PKC-independent, suggesting differential regulation of O2(-) production. An important step in activation of the NADPH oxidase is phosphorylation of the cytosolic p47phox component. In adherent neutrophils, TNF triggered a time-dependent assoc...
Source: Journal of Leukocyte Biology - October 1, 2009 Category: Hematology Authors: Kilpatrick LE, Sun S, Li H, Vary TC, Korchak HM Tags: J Leukoc Biol Source Type: journals

Macrophage differentiation of myeloid progenitor cells in response to M-CSF is regulated by the dual-specificity phosphatase DUSP5.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we sought to isolate genes whose induction by M-CSF is dependent on persistent MAPK activation, thereby being possibly involved in the commitment of myeloid progenitors to macrophage differentiation. Following SSH between cDNA libraries from FD-Fms cells stimulated by M-CSF for 8 h in the presence or the absence of the MEK inhibitor U0126, we isolated DUSP5. DUSP5 expression is induced by M-CSF in various myeloid cells and acts as a specific negative-feedback regulator of ERK1/2. In FD-Fms cells that proliferate and differentiate toward macrophages in response to M-CSF, overexpression of DUSP5 increased M-CS...
Source: Journal of Leukocyte Biology - October 1, 2009 Category: Hematology Authors: Grasset MF, Gobert-Gosse S, Mouchiroud G, Bourette RP Tags: J Leukoc Biol Source Type: journals

Oxidative stress can alter the antigenicity of immunodominant peptides.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
APCs operate frequently under oxidative stress induced by aging, tissue damage, pathogens, or inflammatory responses. Phagocytic cells produce peroxides and free-radical species that facilitate pathogen clearance and can in the case of APCs, also lead to oxidative modifications of antigenic proteins and peptides. Little information is available presently about the consequences of such modifications on the immune response. To model oxidative modification of an immunodominant antigenic peptide, we oxidized the methionine residue of the human CMV pp65495-503 (NLVPMVATV) peptide. Such modifications of an antigenic peptide ...
Source: Journal of Leukocyte Biology - October 1, 2009 Category: Hematology Authors: Weiskopf D, Schwanninger A, Weinberger B, Almanzar G, Parson W, Buus S, Lindner H, Grubeck-Loebenstein B Tags: J Leukoc Biol Source Type: journals

Dynamic alterations in chemokine gradients induce transendothelial shuttling of human T cells under physiologic shear conditions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The direct movement of cells from subendothelial compartments into the bloodstream (intravasation) has been recognized for several decades by histologic and physiologic studies, yet the molecular effectors of this process are relatively uncharacterized. For extravasation, studies based predominantly on static transwell assays support a general model, whereby TEM occurs via chemoattraction toward increasing chemokine concentrations. However, this model of chemotaxis cannot readily reconcile how chemokines influence intravasation, as shear forces of blood flow would likely abrogate luminal chemokine gradient(s). Thus, to...
Source: Journal of Leukocyte Biology - September 30, 2009 Category: Hematology Authors: Lee JY, Buzney CD, Poznansky MC, Sackstein R Tags: J Leukoc Biol Source Type: journals

IL-21 preferentially enhances IL-15-mediated homeostatic proliferation of human CD28+ CD8 memory T cells throughout the adult age span.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
An age-related decline in human immune response is marked by the accumulation of CD28(-) CD8 T cells, which is attributed to repeated antigenic stimulation and to homeostatic proliferation mediated by cytokines such as IL-15. However, the identity of the cytokines that are responsible for the maintenance of CD28 expression is less known. Here, we report the role of IL-21 in the regulation of IL-15-mediated growth and CD28 expression of CD8 memory T cells of young and old donors. We showed that IL-21 drives more IL-15-stimulated cells to enter cell division and to undergo apoptosis. Furthermore, IL-21 preferentially enh...
Source: Journal of Leukocyte Biology - September 30, 2009 Category: Hematology Authors: Nguyen H, Weng NP Tags: J Leukoc Biol Source Type: journals

Pivotal Advance: Heme oxygenase 1 expression by human CD4+ T cells is not sufficient for their development of immunoregulatory capacity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
HO-1 is the only inducible one of three isoenzymes that catalyzes the oxidative degradation of heme. HO-1 is inducible by various cellular stress factors and exerts cytoprotective and immunomodulatory effects. Recent publications demonstrated that HO-1 is constitutively expressed by CD4(+)CD25(+) Tregs and induced in CD4(+)CD25(-) T cells upon FoxP3 transfection. Here, we investigated whether HO-1 was essential and sufficient for human Tregs to exert immunosuppression in vitro. PGJ2 induced pronounced expression of HO-1 in CD4(+)CD25(-) T cells without accompanying FoxP3 induction. Treatment of CD4(+)CD25(-) T cells wi...
Source: Journal of Leukocyte Biology - September 30, 2009 Category: Hematology Authors: Biburger M, Theiner G, Schädle M, Schuler G, Tiegs G Tags: J Leukoc Biol Source Type: journals

Editorial: NKT cells: to suppress or not to suppress, that is the question.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19797301 [PubMed - in process] (Source: Journal of Leukocyte Biology)
Source: Journal of Leukocyte Biology - September 30, 2009 Category: Hematology Authors: Subleski JJ, Ortaldo JR Tags: J Leukoc Biol Source Type: journals

Editorial: Basophil survival and immunomodulatory function are uniquely regulated by a novel MyD88-dependent pathway.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19797302 [PubMed - in process] (Source: Journal of Leukocyte Biology)
Source: Journal of Leukocyte Biology - September 30, 2009 Category: Hematology Authors: Knol EF, Gibbs BF Tags: J Leukoc Biol Source Type: journals

Induction of Th1/Th17 immune response by Mycobacterium tuberculosis: role of dectin-1, mannose receptor, and DC-SIGN.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Mtb influences DC activity and T cell-mediated immune responses. We show that the treatment of immature monocyte-derived DC with Mtb elicited the formation of mature DC, producing TNF-alpha, IL-1beta, IL-6, and IL-23 and instructing CD4(+) cells to secrete IFN-gamma and IL-17. Mtb-induced cytokine release by DC depended on dectin-1 receptor engagement, whereas MR or DC-SIGN stimulation inhibited this process. A selective dectin-1 binding by the receptor agonist glucan was sufficient to enable DC to generate Th1/Th17 lymphocytes, showing features comparable with those induced by Mtb-treated DC. Interestingly, DC-SIGN or...
Source: Journal of Leukocyte Biology - September 21, 2009 Category: Hematology Authors: Zenaro E, Donini M, Dusi S Tags: J Leukoc Biol Source Type: journals

IL-21 and IL-10 have redundant roles but differential capacities at different stages of plasma cell generation from human germinal center B cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we investigated in detail the functional role of IL-21 in the course of GC-B cell differentiation into terminally differentiated PC compared with that of IL-10, a well-known PC differentiation factor. IL-21 had a greater capacity to initiate PC differentiation from CD77(+) centroblasts than IL-10 by strongly inducing PC transcription factors through activation of STAT3; however, IL-10 was more potent than IL-21 in generating CD138(+) PC from CD20(-)CD38(++) plasmablasts in the terminal stage of GC-B cell differentiation. This differential effect of IL-21 and IL-10 was reflected in receptor expression on B ce...
Source: Journal of Leukocyte Biology - September 16, 2009 Category: Hematology Authors: Yoon SO, Zhang X, Berner P, Choi YS Tags: J Leukoc Biol Source Type: journals

The axonal repellent, Slit2, inhibits directional migration of circulating neutrophils.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In inflammatory diseases, circulating neutrophils are recruited to sites of injury. Attractant signals are provided by many different chemotactic molecules, such that blockade of one may not prevent neutrophil recruitment effectively. The Slit family of secreted proteins and their transmembrane receptor, Robo, repel axonal migration during CNS development. Emerging evidence shows that by inhibiting the activation of Rho-family GTPases, Slit2/Robo also inhibit migration of other cell types toward a variety of chemotactic factors in vitro and in vivo. The role of Slit2 in inflammation, however, has been largely unexplore...
Source: Journal of Leukocyte Biology - September 15, 2009 Category: Hematology Authors: Tole S, Mukovozov IM, Huang YW, Magalhaes MA, Yan M, Crow MR, Liu GY, Sun CX, Durocher Y, Glogauer M, Robinson LA Tags: J Leukoc Biol Source Type: journals

Modulation of human plasmacytoid DC function by IFN-{lambda}1 (IL-29).Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The type III family of IFNs displays immunomodulatory and antiviral activity. Each member (IFN-lambda1, -2, and -3) signals through the same heterodimeric receptor complex, which consists of the binding and signaling subunit (IL-28Ralpha) plus the IL-10Rbeta chain. Although the receptor has a wide tissue distribution, the direct effects of IFN-lambda on various immune cell subsets have not been fully characterized. We have identified high levels of IL-28Ralpha mRNA in pDC from peripheral blood and hypothesized that IFN-lambda plays an important role in pDC maturation and development. We show that stimulation of pDC wit...
Source: Journal of Leukocyte Biology - September 15, 2009 Category: Hematology Authors: Megjugorac NJ, Gallagher GE, Gallagher G Tags: J Leukoc Biol Source Type: journals

Enhanced production of IL-17A during zymosan-induced peritonitis in obese mice.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
IL-17A is a proinflammatory cytokine critical for host defense and involved in the pathogenesis of autoimmune disorders. Obesity is associated with chronic low-grade inflammation but also with a heightened acute inflammatory response. We investigated the effect of obesity on IL-17A production using the model of ZY-induced peritonitis. Compared with lean controls, administration of ZY induced a significantly exacerbated inflammatory response in obese leptin-deficient ob/ob mice and in mice with diet-induced obesity (DIO). Levels of IL-17A in the peritoneal fluid in response to ZY were elevated significantly in ob/ob and...
Source: Journal of Leukocyte Biology - September 9, 2009 Category: Hematology Authors: Pini M, Fantuzzi G Tags: J Leukoc Biol Source Type: journals

ABC drug transporters and immunity: novel therapeutic targets in autoimmunity and cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
ABC transporters were identified originally for their contribution to clinical MDR as a result of their capacity to extrude various unrelated cytotoxic drugs. More recent reports have shown that ABC transporters can play important roles in the development, differentiation, and maturation of immune cells and are involved in migration of immune effector cells to sites of inflammation. Many of the currently identified, endogenous ABC transporter substrates have immunostimulating effects. Increasing the expression of ABC transporters on immune cells and thereby enhancing immune cell development or functionality may be bene...
Source: Journal of Leukocyte Biology - September 9, 2009 Category: Hematology Authors: van de Ven R, Oerlemans R, van der Heijden JW, Scheffer GL, de Gruij TD, Jansen G, Scheper RJ Tags: J Leukoc Biol Source Type: journals

Ficolin-1 is present in a highly mobilizable subset of human neutrophil granules and associates with the cell surface after stimulation with fMLP.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Ficolins are soluble molecules that bind carbohydrate present on the surface of microorganisms and function as recognition molecules in the lectin complement pathway. Three ficolins have been identified in humans: ficolin-1, ficolin-2, and ficolin-3. Ficolin-1 is synthesized in monocytes and type II alveolar epithelial cells. Ficolin-1 has been shown to be present in secretory granules of human neutrophils, but it is not known which subset of the neutrophils' secretory granules harbors ficolin-1. To determine the exact subcellular localization of ficolin-1 in neutrophils, recombinant ficolin-1 was expressed in Chinese ...
Source: Journal of Leukocyte Biology - September 8, 2009 Category: Hematology Authors: Rørvig S, Honore C, Larsson LI, Ohlsson S, Pedersen CC, Jacobsen LC, Cowland JB, Garred P, Borregaard N Tags: J Leukoc Biol Source Type: journals

CD4+CD25+ regulatory T cells attenuate hypersensitivity pneumonitis by suppressing IFN-{gamma} production by CD4+ and CD8+ T cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
HP results from the repeated inhalation of environmental antigens; however, the roles of CD4(+)CD25(+) Treg cells in HP are unknown. Therefore, we investigated the functions of CD4(+)CD25(+) Treg cells in SR-induced murine HP. More severe HP was observed in CD4(+)CD25(+) Treg cell-depleted mice than in control mice in terms of histological alterations, inflammatory cell numbers in BALF, and the serum level of SR-specific IgG, which were restored by the adoptive transfer of CD4(+)CD25(+) Treg cells. The CD4(+)CD25(+) Treg cell-depleted mice also showed elevated levels of IFN-gamma, TGF-beta, and reduced IL-4 production ...
Source: Journal of Leukocyte Biology - September 8, 2009 Category: Hematology Authors: Park Y, Oh SJ, Chung DH Tags: J Leukoc Biol Source Type: journals

Development and function of IL-10 IFN-{gamma}-secreting CD4+ T cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
IL-10 IFN-gamma-secreting CD4(+) T cells were first found in the early 1990s. They are suppressive T cells able to inhibit cytotoxic T lymphocytes. These cells (Foxp3-T bet(+)) have a similar function but are distinct from conventional Tregs. The production of IL-10 in these cells requires IL-27 and TGF-beta and was regulated by several signal pathways including Notch, STAT, and NF-kappaB. The crosstalk among these pathways is critical for the generation and function of these cells. IL-10 IFN-gamma-secreting CD4(+) T cells are activated in chronic infection and are responsible for prolonged infection. Thus, their modul...
Source: Journal of Leukocyte Biology - September 8, 2009 Category: Hematology Authors: Chen J, Liu XS Tags: J Leukoc Biol Source Type: journals

Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract The microenvironment of solid tumors is characterized by a reactive stroma with an abundance of inflammatory mediators and leukocytes, dysregulated vessels and proteolytic enzymes. TAM, major players in the connection between inflammation and cancer, summarize a number of functions (e.g., promotion of tumor cell proliferation and angiogenesis, incessant matrix turnover, repression of adaptive immunity), which ultimately have an important impact on disease progression. Thus, together with other myeloid-related cells present at the tumor site (Tie2 macrophages and MDSCs), TAM represent an attractive target of no...
Source: Journal of Leukocyte Biology - September 8, 2009 Category: Hematology Authors: Solinas G, Germano G, Mantovani A, Allavena P Tags: J Leukoc Biol Source Type: journals

Characterization of Cdk9 T-loop phosphorylation in resting and activated CD4+ T lymphocytes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The cellular kinase complex P-TEFb is composed of Cdk9 and cyclin T, and it is required for expression of most protein-coding genes by RNAP II. Cdk9 has been shown recently to be activated in cis by autophosphorylation of Thr186 in its T-loop. Using a phosphospecific Cdk9 antibody, we examined the level of Cdk9 T-loop phosphorylation in resting and activated CD4(+) T lymphocytes. Cdk9 T-loop phosphorylation was found to be low-to-undetectable in resting CD4(+) T lymphocytes, and upon activation by distinct stimuli, there is a rapid (<1 h) increase in pCdk9 that does not require protein synthesis. The low level of Cd...
Source: Journal of Leukocyte Biology - September 8, 2009 Category: Hematology Authors: Ramakrishnan R, Dow EC, Rice1 AP Tags: J Leukoc Biol Source Type: journals