Abstract:
:The effects of the carbocyclic nucleoside MDL 201,112 and the purine nucleoside adenosine on the interferon-gamma (IFN-gamma)-induced priming of macrophages (m phi s) for the respiratory burst and major histocompatibility class II (MHC class II) Ia+ antigen expression were compared. Priming of purified, peritoneal m phi s from Lewis (LEW/N) rats for 18 h with recombinant rat IFN-gamma (rRaIFN-gamma) in the presence of either adenosine (100 microM) or MDL 201,112 (10 microM) resulted in a fourfold decrease in superoxide anion (O2-) production after stimulation with opsonized zymosan. Both agents were effective even when added 2 or 4 h after rRaIFN-gamma treatment. Peritoneal m phi s from LEW/N rats stimulated with LPS/rRaIFN-gamma were observed to secrete immunoreactive and bioactive TNF-alpha over 18 h in vitro and this cytokine could be dose-dependently inhibited by MDL 201,112. MDL 201,112 did not bind to classical A1 or A2 receptors on rat brain homogenates. Physiological levels of adenosine deaminase, or treatment with the nucleoside transport inhibitor dipyridamole, reversed the effects of adenosine; however, these agents at physiological concentrations had little or no effect on the inhibition of O2- release mediated by MDL 201,112. Furthermore, incubation of LEW/N m phi s for 18 h in vitro with rRaIFN-gamma resulted in significant enhancement of MHC class II Ia+ antigen expression, and these levels could be blocked by nearly 50% by either MDL 201,112 (10 microM) or adenosine (100 microM). MDL 201,112 and adenosine were also effective in decreasing m phi opsonized zymosan-stimulated O2- levels and MHC class II Ia+ antigen expression in vivo. The effects of MDL 201,112 on the down-regulation of heat-killed M. tuberculosis-activated LEW/N m phi MHC class II Ia+ antigen expression in vitro appear to be mediated by a novel pathway, because there was no rank order of potency of ADO A1 or A2 agonist/antagonists (CCPA, NECA, XAC, or CPT) in our in vitro system. In summary, our data provide compelling evidence that immunoregulatory carbocyclic nucleoside analogues such as MDL 201,112 or adenosine appear to regulate LEW/N rat m phi activation through novel molecular mechanisms and may have important therapeutic implications for acute and chronic inflammatory diseases.
journal_name
J Leukoc Bioljournal_title
Journal of leukocyte biologyauthors
Edwards CK 3rd,Watts LM,Parmely MJ,Linnik MD,Long RE,Borcherding DRdoi
10.1002/jlb.56.2.133subject
Has Abstractpub_date
1994-08-01 00:00:00pages
133-44issue
2eissn
0741-5400issn
1938-3673journal_volume
56pub_type
杂志文章abstract::Recent studies have shown that proinflammatory cytokines damage rodent neural precursor cells (NPCs), a source of self-renewing, multipotent cells that play an important role in the developing as well as adult brain. In this study, the effects of tumor necrosis factor alpha (TNF-alpha) on cytokine and chemokine produc...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0405221
更新日期:2005-12-01 00:00:00
abstract::During B-cell differentiation, the gene expression of B-cell differentiation-related transcription factors must be strictly controlled by epigenetic mechanisms including histone acetylation and deacetylation, to complete the differentiation pathway. GCN5, one of the most important histone acetyltransferases, is involv...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0413232
更新日期:2014-03-01 00:00:00
abstract::Neutrophils are indispensable in the innate immune defense against invading microorganisms. Neutrophils contain SVs and several subsets of granules that are essential for their function. Proteins present in neutrophil SVs and granules are synthesized during terminal granulopoiesis in the bone marrow. The heterogeneity...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1212619
更新日期:2013-10-01 00:00:00
abstract::Phagocytosis is the process whereby cells engulf large particles, usually over 0.5 micro m in diameter. Phagocytosis is triggered by the interaction of opsonins that cover the particle to be internalized with specific receptors on the surface of the phagocyte. The best-studied phagocytic receptors include the Fc recep...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:
更新日期:2002-12-01 00:00:00
abstract::Secreted IgM (sIgM) is a multifunctional evolutionary conserved antibody that is critical for the maintenance of tissue homeostasis as well as the development of fully protective humoral responses to pathogens. Constitutive secretion of self- and polyreactive natural IgM, produced mainly by B-1 cells, provides a circu...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/JLB.3RI0519-161R
更新日期:2019-11-01 00:00:00
abstract::Dysregulated Ca(2+) handling is prevalent during sepsis and postulated to perpetuate the aberrant inflammation underlying subsequent organ dysfunction and death. The signal transduction cascades mediating these processes are unknown. Here, we identify that CaMKIα mediates the Mϕ response to LPS in vitro and the inflam...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0510286
更新日期:2011-08-01 00:00:00
abstract::TKs are intracellular signaling molecules essential for cell homeostasis. Inhibition of TKs is used in treatment of malignancies and diabetes mellitus. The present study evaluated the role of Flt3 in antigen-induced arthritis. Mice were immunized with mBSA, and arthritis was induced by an i.a. injection of mBSA. Treat...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1110640
更新日期:2011-10-01 00:00:00
abstract::The production of IL-12 by macrophages/dendritic cells (Mphi/DC) is mediated either by a T cell-dependent pathway that is induced primarily by the interaction of CD40 ligand (CD40L) on activated T cells with CD40 on IL-12-producing cells or by a T cell-independent pathway that is induced by bacteria or bacterial produ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.61.1.80
更新日期:1997-01-01 00:00:00
abstract::PGE(2) and other cAMP-elevating agents are known to down-regulate most functions stimulated by fMLP in human polymorphonuclear neutrophils. We reported previously that the inhibitory potential of PGE(2) resides in its capacity to suppress fMLP-stimulated PI-3Kgamma activation via the PGE(2) receptor EP(2) and hence, t...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0406256
更新日期:2007-06-01 00:00:00
abstract::Although all the cells in an organism contain the same genetic information, differences in the cell phenotype arise from the expression of lineage-specific genes. During myelopoiesis, external differentiating signals regulate the expression of a set of transcription factors. The combined action of these transcription ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1002/jlb.63.4.405
更新日期:1998-04-01 00:00:00
abstract::4-1BB is a member of the TNFR superfamily, which contributes to the activation of signaling pathways required for the survival of activated and memory T cells. We have shown previously that TRAF1, an adaptor protein recruited to 4-1BB, is required for 4-1BB-mediated CD8 T cell survival in vivo. With the use of a prote...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1112579
更新日期:2013-05-01 00:00:00
abstract::Polymorphonuclear leukocytes (PMN) play an important role in inflammation, immune responses, and tissue repair by secreting interleukin- 1 beta (IL-1 beta). We investigated the regulation of IL-1 beta gene expression in human PMN treated with granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF induced IL...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.59.4.598
更新日期:1996-04-01 00:00:00
abstract::An acute inflammatory response requires that circulating monocytes bind to and migrate across the endothelium of the vessel wall to gain access to inflamed sites. Various mediators of inflammation--cytokines and chemoattractants--have been shown to initiate and regulate the margination and extravasation of monocytes. ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:
更新日期:1993-10-01 00:00:00
abstract::The liver contains a unique repertoire of immune cells and a particular abundance of NK cells. We have found that CD11c defines a distinct subset of NK cells (NK1.1(+)CD3(-)) in the murine liver whose function was currently unknown. In naïve animals, CD11c(+) liver NK cells displayed an activated phenotype and possess...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0408256
更新日期:2008-10-01 00:00:00
abstract::Complement component C1q is a member of a family of soluble proteins called defense collagens, which are important in host defense and apoptotic cell clearance. Failure to efficiently clear apoptotic cells in the absence of C1q is associated with autoimmunity. Here, we review the literature describing a central role f...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章,评审
doi:10.1189/jlb.0212099
更新日期:2012-09-01 00:00:00
abstract::We have shown previously that the cellular proteins 47b and 71/73 could be used to construct phenotypes that distinguish among bone marrow culture-derived (BMCD) macrophages that were either unstimulated or primed by gamma interferon or fully activated for tumor cell killing by gamma interferon in combination with lip...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.42.3.213
更新日期:1987-09-01 00:00:00
abstract::Several lines of evidence support the concept that NK cells play an important role in control of hepatitis C virus (HCV) infection via cytokine secretion and cytotoxicity. IL-7 is a homeostatic cytokine with a role in T cell development, activation, proliferation, and cytokine secretion. The IL-7Rα chain [cluster of d...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.5A1116-456R
更新日期:2017-07-01 00:00:00
abstract::Besides their growth-inhibiting and differentiation-inducing properties, retinoids have been shown to exert immunomodulatory and anti-inflammatory functions by mechanisms that are not well understood. Tumor necrosis factor-alpha (TNF), a cytokine produced by mononuclear phagocytes, has been shown to be an important me...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.55.3.336
更新日期:1994-03-01 00:00:00
abstract::Mac-1 (CD11b/CD18) is known to be involved in neutrophil (PMN) adhesion to endothelial cells and extracellular matrix. Although antibodies to CD 18 are being tested for therapy in humans, their role in PMN migration through the extracellular matrix is unknown. We used direct visualization to quantify PMN motility thro...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.65.3.356
更新日期:1999-03-01 00:00:00
abstract::The adhesion and degranulation promoting adaptor protein (ADAP) is a multifunctional scaffold involved in many different signaling pathways that are important for the function of T cells, including the inside-out and outside-in signaling of integrins, the activation of NF-κB, and the subsequent production of proinflam...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.1A0216-090RR
更新日期:2017-02-01 00:00:00
abstract::Mono-Mac-6 (MM6) human monocytes ingest IgG-opsonized particles better than other human cell lines. We compared the phagocytic signaling pathway in MM6 with human monocytes. MM6 expressed FcgammaRI at levels similar to monocytes, whereas FcRgammaII expression was approximately double. MM6 ingested IgG-opsonized erythr...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.65.6.854
更新日期:1999-06-01 00:00:00
abstract::Dendritic cell (DC) and DC-derived exosomes (EXO) have been used extensively for tumor vaccination. However, its therapeutic efficiency is limited to only production of prophylactic immunity against tumors. T cells can uptake DC-released EXO. However, the functional effect of transferred exosomal molecules on T cells ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0407249
更新日期:2007-10-01 00:00:00
abstract::Carcinoembryonic antigen (CEA), a member of the immunoglobulin supergene family, is recognized by a specific 80-kd receptor on Kupffer cells and alveolar macrophages. Peritoneal macrophages were harvested from male Sprague-Dawley rats 72 h after intraperitoneal injection with thioglycolate broth and from unstimulated ...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1002/jlb.51.5.466
更新日期:1992-05-01 00:00:00
abstract::Mer signaling participates in a novel inhibitory pathway in TLR activation. The purpose of the present study was to examine the role of Mer signaling in the down-regulation of TLR4 activation-driven immune responses in mice, i.t.-treated with LPS, using the specific Mer-blocking antibody. At 4 h and 24 h after LPS tre...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0611289
更新日期:2012-06-01 00:00:00
abstract::Tumor-associated eosinophilia has been observed in numerous human cancers and several tumor models in animals; however, the details surrounding this eosinophilia remain largely undefined and anecdotal. We used a B16-F10 melanoma cell injection model to demonstrate that eosinophil infiltration of tumors occurred from t...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0106027
更新日期:2006-06-01 00:00:00
abstract::The cytosolic adaptor molecule SKAP-HOM, similar to the T cell-specific homologue SKAP55, interacts directly with ADAP, and both molecules are involved in inside-out signaling. Previous studies have shown that in the absence of SKAP-HOM, antigen receptor-triggered integrin-mediated adhesion is impaired severely in B c...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0608344
更新日期:2009-07-01 00:00:00
abstract::Anti-proteinase-3 (anti-PR3) or anti-myeloperoxidase (anti-MPO) antibodies are capable of activating human neutrophils primed by TNF-alpha in vitro. We described previously the involvement of FcgammaRIIa and beta(2) integrins in this neutrophil activation. In the literature, the requirement of TNF priming has been att...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:10.1189/jlb.0304144
更新日期:2006-12-01 00:00:00
abstract::Radiation-induced chimeric mice were used to study the origin of pulmonary alveolar macrophages. Unlike in other studies, these radiation chimeras were prepared by using a special fractionated irradiation regimen to minimize the killing of alveolar macrophage colony-forming cells, putative local stem cells. For this s...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:1987-11-01 00:00:00
abstract::Previously, we described a novel glycosylphosphatidyl inositol (GPI)-anchored glycoprotein (designated GPI-80) on human neutrophils and monocytes that may regulate beta(2) integrin-dependent neutrophil adherence and migration. However, the mechanism regulating beta(2) integrin remains to be clarified. To study this, w...
journal_title:Journal of leukocyte biology
pub_type: 杂志文章
doi:
更新日期:2002-02-01 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