Abstract:
:SIRS is associated with lymphopenia, and prolonged lymphopenia of septic patients has been associated with increased mortality risk. We hypothesize that elevated adenosine during SIRS down-regulates Gi-coupled A1R, which signals an effect that sensitizes a cAMP-dependent lymphotoxic response. In this study, we evaluate the role of adenosine in SIRS-mediated lymphopenia and impaired IL-15 production. Cecal ligation and puncture was used to induce sepsis-associated SIRS in mice. BMDCs were cultured and used to measure the effect of adenosine on IL-15. We found that A1R mRNA levels were significantly down-regulated and A1R-dependent Gi activity was abolished in T cells of septic mice. In accordance, cAMP was elevated in isolated T cells from cecal ligation and puncture compared with sham-treated mice. Similar to septic mice, leukopenia was evident in sham A1R-KO mice, after treatment with the A1R antagonist (8-cyclopentyl-1,3-dipropylxanthine), or after A1R desensitization. In contrast, A2AR-KO mice were protected from leukopenia. In addition, we observed that septic A1R-KO mice exhibited low IL-15 levels. Cultured BMDC agonists of A2AR and A2BR inhibited IL-15 production and adenosine blocked IL-15-dependent proliferation of cytotoxic T cells that were cocultured with stimulated BMDCs. To conclude, we suggest that SIRS-associated lymphopenia is initiated by A1R desensitization and adenosine-mediated inhibition of IL-15 production is part of the mechanism that accounts for the delay in leukopenia recovery in patients with severe sepsis. Interference with adenosine signaling may thus be potentially beneficial for septic patients with leukopenia.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Riff R,Cohen Y,Eini-Rider H,Naamani O,Mazar J,Haviv YS,Chaimovitz C,Douvdevani Adoi
10.1189/jlb.3A0816-345RRsubject
Has Abstractpub_date
2017-07-01 00:00:00pages
95-103issue
1eissn
0741-5400issn
1938-3673pii
jlb.3A0816-345RRjournal_volume
102pub_type
杂志文章abstract::The basal presence of immunologically potent cells within the intestinal muscularis externa and their functional significance is unclear. Our aim was to investigate the basal distribution of various leukocyte populations within the rat jejunal muscularis. In addition, we sought to immunohistochemically phenotype the m...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.63.6.683
更新日期:1998-06-01 00:00:00
abstract::As part of a study to identify novel genes associated with macrophage activation, we have cloned a new member of the transforming growth factor beta (TGF-beta) superfamily designated macrophage inhibitory cytokine 1 (MIC-1). MIC-1 is synthesized as a 62-kDa intracellular protein, which, after cleavage by a furin like ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/jlb.65.1.2
更新日期:1999-01-01 00:00:00
abstract::Vascular occlusion is the main cause of the morbidity and mortality observed in patients with sickle cell disease (SCD). Increasing evidence indicates that (activated) neutrophils could play an important role in the initiation and propagation of vaso-occlusive processes in SCD. In this study, the activation state of n...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.66.3.411
更新日期:1999-09-01 00:00:00
abstract::Stimulation of phagocytic leukocytes with chemotactic factors results in transient acidification, followed by alkalinization of the cytosol. Human monocytes are known to alter their functional responses to the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP) in a complex fashion as they mature in vitr...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.53.6.673
更新日期:1993-06-01 00:00:00
abstract::Serum MBP, also known as MBL, is a C-type lectin that is known to be a soluble host defense factor involved in innate immunity. It has been well established that dying microbes and apoptotic cells release highly viscous DNA that induces inflammation and septic shock, and apoptotic cells display fragmented DNA on their...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1008674
更新日期:2009-09-01 00:00:00
abstract::The aim of this study was to test the hypothesis whether MERTK, which is up-regulated in human DCs treated with immunosuppressive agents, is directly involved in modulating T cell activation. MERTK is a member of the TAM family and contributes to regulating innate immune response to ACs by inhibiting DC activation in ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.3A0714-334R
更新日期:2015-04-01 00:00:00
abstract::Pulmonary fibrosis is the end point of a chronic inflammatory process characterized by leukocyte recruitment and activation, fibroblast proliferation, and increased extracellular matrix production. Previous studies of models of pulmonary fibrosis have investigated the role of cytokines in the evolution of the fibrotic...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/jlb.57.5.782
更新日期:1995-05-01 00:00:00
abstract::ARDS is a severe form of lung injury characterized by increased permeability of the alveolar capillary membrane, diffuse alveolar damage, the accumulation of proteinaceous interstitial and intra-alveolar edema, and the presence of hyaline membranes. These pathological changes are accompanied by physiological alteratio...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.0209087
更新日期:2009-11-01 00:00:00
abstract::The immunosuppressive activity of interleukin-10 (IL-10) makes this cytokine a potentially important clinical tool to reduce inflammatory responses in various diseases. Its efficacy as a therapeutic modality is dependent on the responsiveness of immune cells. We report that macrophages from mice chronically infected w...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2001-10-01 00:00:00
abstract::Macrophages play an important role in a wide variety of physiologic and pathologic processes. Plasticity and functional polarization are hallmarks of macrophages. Macrophages commonly exist in two distinct subsets: classically activated macrophages (M1) and alternatively activated macrophages (M2). M2b, a subtype of M...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/JLB.3RU1018-378RR
更新日期:2019-08-01 00:00:00
abstract::Introduction of alloantigens into the AC induces a form of immune tolerance known as ACAID, which induces antigen-specific CD8+ Tregs, contributing to ocular immune privilege by down-regulating immune responses. Recent evidence suggests IFN-γ is needed for the suppressive function of CD8+ ACAID Tregs. This study teste...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0311173
更新日期:2012-03-01 00:00:00
abstract::The membrane fusion events observed during neutrophil degranulation are important aspects of the immunoregulatory system. In an attempt to understand the regulation of granule-plasma membrane fusion, we have begun characterizing human neutrophil cytosol for fusion activity, finding that 50% of the fusogenic activity c...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.63.3.331
更新日期:1998-03-01 00:00:00
abstract::The Fc gamma receptor IIB (FcγRIIB/CD32B) was generated million years ago during evolution. It is the sole inhibitory receptor for IgG, and has long been associated with the regulation of humoral immunity and innate immune homeostasis. However, new and surprising functions of FcγRIIB are emerging. In particular, FcγRI...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/JLB.2MIR0917-354R
更新日期:2018-02-06 00:00:00
abstract::Absence of lymph nodes in nonmammalian species, expression of MHCII by APCs in the periphery, and the recent findings that T cells can change their polarization status after presentation in the lymph nodes imply a role for MHCII-mediated presentation outside the organized lymphoid tissue. This study shows that MHCII(+...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0310161
更新日期:2010-09-01 00:00:00
abstract::Although a number of chemokine receptors display coreceptor activities in vitro, chemokine receptor 5 (CCR5) and CXC chemokine receptor 4 (CXCR4) remain the major coreceptors used by the human immunodeficiency virus type 1 (HIV-1). In this study, we used an envelope-mediated fusion assay to demonstrate low CCR4 corece...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2002-11-01 00:00:00
abstract::Leukocyte trafficking from the blood into the tissues represents a key process during inflammation and requires multiple steps mediated by adhesion molecules and chemoattractants. Inflammation has a detrimental role in several diseases, and in such cases, the molecular mechanisms controlling leukocyte migration are po...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.0710432
更新日期:2011-04-01 00:00:00
abstract::CD5L, a soluble protein belonging to the SRCR superfamily, is expressed mostly by macrophages in lymphoid and inflamed tissues. The expression of this protein is transcriptionally controlled by LXRs, members of the nuclear receptor family that play major roles in lipid homeostasis. Research undertaken over the last de...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.3RU0215-074R
更新日期:2015-08-01 00:00:00
abstract::Polymorphonuclear leukocytes (PMNs) exert most of their physiological functions while adherent to surfaces rather than in suspension. PMN adhesion is largely dependent on the function of the beta 2 integrins, CD11a,b,c/CD18. We mimicked engagement of beta 2 integrins by antibody cross-linking of CD18 on isolated human...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.56.5.625
更新日期:1994-11-01 00:00:00
abstract::To understand the modulation and the behavior of glycocalyx elements during adhesion, we explored one of its components, the CD43 molecule, on human monocytic THP-1 cells exposed to cytokine stimulation and its redistribution during heterotypic adhesion to opsonized erythrocytes. First we demonstrated by immunofluores...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.61.5.609
更新日期:1997-05-01 00:00:00
abstract::Monocyte chemoattractant protein-1 (MCP-1, CCL2) is a mediator of inflammation that has been implicated in the pathogenesis of a wide variety of human diseases. CCR2, a heterotrimeric G-coupled receptor, is the only known receptor that functions at physiologic concentrations of MCP-1. Despite the importance of CCR2 in...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0903421
更新日期:2004-06-01 00:00:00
abstract::Ly-49 receptors regulate mouse natural killer cell functions. Members of the polymorphic Ly-49 multigene family recognize specific alleles of major histocompatibility complex class I (MHC I) or MHC I-like proteins. Previous studies have provided insight into the nature of Ly-49A and -C interaction with their high-affi...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0704407
更新日期:2005-05-01 00:00:00
abstract::Hematopoietic cell differentiation takes place in phenotypically recognizable stages characterized by morphology as well as by the expression of enzymes and surface markers. It is recognized that differentiation results from an interaction of environmental cues, such as cytokines and hormones, with internal cellular p...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.67.4.559
更新日期:2000-04-01 00:00:00
abstract::Type I IFNs are used for treating viral, neoplastic, and inflammatory disorders. The protein products encoded by IFN-stimulated genes (ISGs) likely mediate clinical effects of IFN in patients. Macroarray assays, used for studying ISG induction in IFN-treated patients, comprise genes identified predominantly through an...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0507273
更新日期:2007-11-01 00:00:00
abstract::Neutrophil apoptosis leads to macrophage ingestion of intact senescent neutrophils. This may represent a neutrophil removal mechanism that is important both in the control of inflammatory tissue injury and for the normal resolution processes of inflammation. Because apoptosis is likely to be a key control process in c...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:1993-10-01 00:00:00
abstract::LPS has been widely used to induce inflammatory pain, attributing to production of inflammatory cytokines and sensitization of nociceptors. Paeoniflorin (PF) possesses anti-nociceptive property, but its effect on LPS-induced inflammatory pain has not been investigated. In this study, we aimed to investigate the analge...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/JLB.3MA0220-355R
更新日期:2020-07-01 00:00:00
abstract::We have developed a method that enables the rates of phagocytosis and killing of bacteria by neutrophils to be measured in a single assay. Neutrophils were incubated with bacteria, and at specific intervals were separated from uningested bacteria by low speed centrifugation. Rates of phagocytosis and killing were calc...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.55.2.147
更新日期:1994-02-01 00:00:00
abstract::CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. Reverse transcriptase-polymerase chain reaction analysis indicated that all three CD163 variants are substantially expressed in...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1005602
更新日期:2006-04-01 00:00:00
abstract::Recombinant fusion proteins consisting of the extracellular domain of immunoregulatory proteins and the constant domain of immunoglobulin G (IgG) are a novel class of human therapeutics. IgG isoforms exert different levels of immune effector functions, such as complement lysis and antibody-dependent cell cytotoxicity ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2002-09-01 00:00:00
abstract::To assess the effect of hypoxemia on the responses of polymorphonuclear neutrophils (PMN) during an inflammatory response, rats were maintained in a low F1O2 atmosphere (9% O2) or room air for 12 h before intrathoracic injection of carrageenin or intradermal injections of agonists. After 4 h, hypoxemic rats had 50% mo...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.67.6.785
更新日期:2000-06-01 00:00:00
abstract::Maturation of cells of the mononuclear phagocyte lineage from bone marrow precursors to tissue macrophages (MAC) via circulating blood monocytes (MO) is a multistep process only partially understood. Similarly, MAC differentiation can be observed if MO are cultured in vitro. In an attempt to further characterize molec...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.60.4.540
更新日期:1996-10-01 00:00:00