摘要:

AbstractMembrane receptors for the Fc portion of immunoglobulin G (IgG) antibodies (FcγRs) are expressed on almost every type of hematopoietic cells, where they mediate a wide variety of effector functions. A high degree of structural heterogeneity exists among FcγRs. The biological significance of such heterogeneity is unknown, since the structural diversity does not appear to be reflected in the binding specificity nor in the effector functions that each distinct receptor is able to mediate. Recent work has emphasized the essential role of protein tyrosine phosphorylation in the initiation of trans‐membrane signaling by these receptors. In this article we review the role of protein tyrosine phosphorylation in signal transduction by the different types of FcγRs in order to assess to what extent the structural heterogeneity of this receptor family is related to different activation pathways utilized by each of its members.J. Leukoc. Biol. 60: 433–440; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.4.433

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractCytokines that bind to the interleukin‐2 (IL‐2) receptor common gamma chain (γc), including IL‐2, IL‐4, IL‐7, IL‐9, and IL‐15, are important for the growth and differentiation of T and B lymphocytes, natural killer cells, macrophages, and monoctyes. These cytokines have overlapping biological effects that in part result from the use of the shared receptor subunit γc. Recently it has become clear that these cytokines activate a number of important intracellular signaling molecules, including the Janus kinases JAK1 and JAK3 and members of the transcription factor family of signal transducers and activators of transcription (STATs). The discovery of these signaling pathways has led to important new insights into their role in lymphocyte maturation, as it has emerged that mutations in the genes encoding both γc and JAK3 result in similar forms of severe combined immunodeficiency (SCID). In this review we examine the structure and function of cytokine receptors and the signaling pathways involved in their regulation of gene expression. Furthermore, we discuss recent advances that have led to a better understanding of how cytokines elicit intracellular responses, as well as their role in normal lymphoid development.J. Leukoc. Biol. 60: 441–452; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.4.441

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractWe injected125I‐pro‐macrophage‐stimulating protein (pro‐MSP) intravenously into normal mice to determine its clearance from the circulation and to test for conversion of pro‐MSP to the biologically active heterodimer in the absence of inflammation or tissue injury. Pro‐MSP was cleared from the circulation with a half‐life of approximately 100 min. This rapid clearance was not peculiar to125I‐pro‐MSP, since clearance rates of unlabeled pro‐MSP and of125I‐bovine serum albumin were comparable. The liver was the major locus of radioactivity 10–20 min after the intravenous injection of125I‐pro‐MSP. By 90 min, over 60% of total recovered radioactivity was in the small intestine. Reflecting gastrointestinal transit, counts decreased in the small intestine and appeared in the colon by 180 min. Essentially all counts in urine and feces obtained at later times were soluble in trichloracetic acid. These findings reflected rapid hepatic proteolysis of pro‐MSP to fragments undetectable by antibody to pro‐MSP; within 20 min after intravenous administration, immunoprecipitable counts were only 22% of the total liver extract radioactivity. Comparison of sodium dodecyl sulfate‐polyacrylamide gel electrophoresis and radioautography data for immunoprecipitated plasma and. liver extract revealed no evidence for hepatic conversion of pro‐MSP to MSP. Thus, the hepatic catabolic pathway of pro‐MSP is degradative and don not yield mature MSP. The results support our view that MSP is not released into the circulation but is generated at specific extravascular loci by pro‐MSP convertases. J.Leukoc. Biol. 60: 453–458; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.4.453

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractAbuse of nitrite inhalants, widespread among male homosexuals, has been identified by epidemiological studies as an independent risk factor for AIDS and for Kaposi's sarcoma. Subchronic exposure of mice to inhaled isobutyl nitrite was previously found to impair the tumoricidal activity of peritoneal macrophages. Because inhalants would be expected to have the greatest effects on cells in the lung, alveolar macrophages from exposed mice were examined in this study. Mice were exposed to 900 ppm isobutyl nitrite in an inhalation chamber for 45 min/day for 14 days. Following this treatment, the lungs of exposed mice had large increases in ccllularity, both in the alveolar septa and within the alveoli. Broncho alveolar lavages also contained increased numbers of cells. Alveolar macrophages collected from treated mice had increased tumoricidal activity compared with controls and produced higher levels of inducible nitric oxide and tumor necrosis factor‐α (TNF‐α), The frequency of alveolar cells secreting TNF‐α was increased ninefold in mice exposed to the inhalant. Cell influx into the lung, as indicated by the presence of red blood cells in lung lavages, was evident after only a single 45‐min exposure to inhaled isobutyl nitrite at doses as low as 300 ppm.J. Leukoc. Biol. 60: 459–464; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.4.459

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractIn vivo, dendritic cells (DC) reside in direct proximity to extracellular matrix (ECM) proteins. Because ECM proteins affect morphology and function of a number of cell types, this study investigated potential effects of ECM proteins on functional properties of DC. DC were generated from murine bone marrow cultures, supplemented with granulocyte‐macrophage colony‐stimulating factor, and subsequently cultured on tissue culture plates coated with various ECM proteins. Among the ECM proteins tested, collagen (COL) up‐regulated the T cell stimulatory capacity of DC. This effect was accompanied by sustained surface expression of the co‐stimulatory molecule heat stable antigen on DC and by enhanced release of interleukin‐1 and interleukin‐6, respectively. Because fibronectin or solubilized COL were unable to cause similar changes in DC phenotype or function, we conclude that adherence to COL interferes specifically with DC function. These data suggest that ECM proteins may be involved in regulation of DC phenotype as well as in their functional activation.J. Leukoc. Biol. 60: 465–472; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.4.465

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractNitric oxide has been implicated as an important effector molecule involved in tumor cell growth and cytotoxicity. In these studies we examined mechanisms regulating nitric oxide production by hamster tumor cells. Cocultures of hamster alveolar macrophages (HAM) and spontaneously transformed hamster embryonic fibroblasts (STHE cells) produced significant quantities of nitric oxide in response to lipopolysaccharide (LPS). Culture supernatants from HAM treated with LPS also stimulated nitric oxide production by STHE cells, whereas tumor cell culture supernatants had no effect on HAM. These data, together with the findings that paraformaldehyde treatment of STHE cells, but not macrophages, completely abrogated nitric oxide production in the cocultures demonstrate that the tumor cells were the source of this mediator. In contrast to STHE cells, STHE‐83/20 cells, a highly malignant variant, did not produce nitric oxide in response to HAM or HAM culture supernatants even in the presence of LPS. Both anti‐tumor necrosis factor‐α (TNF‐α) and antiinterleukin‐1α (IL‐1α) antibodies inhibited HAM‐induced nitric oxide production by STHE cells. However, the kinetics of their effects were different. Moreover, although the nitric oxide stimulating activity in HAM culture supernatants was abrogated by anti‐TNF‐α antibody, it was only minimally reduced by anti‐IL‐1α antibody. These data demonstrate that TNF‐α and IL‐1α play distinct roles in induction of nitric oxide synthesis in STHE cells. HAM were also found to suppress proliferation of STHE cells, an effect that was inhibited by anti‐TNF‐α antibody, but notNG‐monomethyl‐l‐arginine, which blocks nitric oxide synthase. Abrogation of macrophage‐induced cytostasis in STHE cells by anti‐TNF‐α antibody was associated with decreased nitric oxide production. Thus TNF‐α released by macrophages may indirectly activate STHE cells for nitric oxide synthesis by suppressing tumor cell proliferation.J. Leukoc. Biol. 60:473–479; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.4.473

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractRat peritoneal neutrophils stimulated byN‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP) produce an aggregation response that can be inhibited by prostaglandin E2(PGE2) with an IC50value of 2.6 10‐9M. Although PGE2can stimulate [3H]cAMP production in neutrophils (EC50 4.3 10‐8M), the anti‐aggregation response cannot be significantly attenuated by inhibitors of adenylate cyclase or protein kinase A, neither can it be potentiated by inhibition of phosphodiesterase activity. Despite these observations, it still remains possible that PGE2‐mediated inhibition of rat neutrophil aggregation is a cAMP‐dependent response mediated by highly localized changes in neutrophil cAMP. The inhibitory effect of PGE2 does not appear to depend on effects on intracellular calcium or KATPchannels. Similarities exist between PGE2and the profile of activity of phosphatidylinositol 3‐kinase (PI 3‐kinase) inhibitors, suggesting that PI 3‐kinase is a possible target for PGE2action in rat neutrophils.J. Leukoc. Biol. 60s 480–486; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.4.480

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractKupffer cells (KC) are the phagocytic macrophages of the liver. The rare earth metal, gadolinium (GdCl3), is a lanthanide, which, after phagocytosis by the KC, has been found to alter various aspects of KC physiology. In this study, we describe for the first time that the in vivo administration of GdCl3to rate decreases the release of NO by isolated rat KC in response to lipopolysaccharide. Western blot analysis shows decreased expression of both imlucible nitric oxide synthase as well as total cellular calmodulin after GdCl3treatment. Possible mechanisms for this phenomenon are suggested.J. Leukoc. Biol60: 487–492; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.4.487

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractEosinophil adhesion and degranulation appear to be associated with cell death. Eosinophils bound avidly and degranulated with secretory immunoglobulin A (slgA)‐ and IgG‐coupled Sepharose 4B beads but bound poorly and did not degranulate with ovalbumin beads. Through the use of dye staining, we found that about 50% of the bound eosinophils were dead by 4 h, regardless of the protein coating. Colchicine and reduced calcium concentration inhibited binding to beads and eosinophil degranulation in a concentration‐dependent manner but did not decrease the percentages of dead bound eosinophils. Electron microscopy showed that eosinophils bound to and spread over bead surfaces. Typical granule exocytosis with release of membrane‐free granules occurred in about 20% of bound eosinophils. Eosinophil degeneration and lysis with release of membrane‐coated granules occurred in about 50% of bound eosinophils; often only membrane‐bound granules were present. Therefore, bound eosinophils degranulate both by classical exocytosis and by release after cytolytic degeneration. By increasing the numbers of bound cells, both IgG and sIgA increase the numbers of dying cells,J. Leukoc. Biol. 60: 493–501; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.4.493

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractMicroglia are the resident macrophages of the brain and as such are active participants in immune responses in the central nervous system. Normal resting microglia express low levels of MHC class I and class II antigens and do not produce proinflammatory cytokines. However, microglial immune functions are induced in areas of infection or injury. To understand regulation of cytokines that are secreted by and act upon microglia, we examined production of interleukin (IL) ‐12, tumor necrosis factor‐α (TNF‐α), and nitric oxide (NO) by lipopolysaccharide (LPS)‐stimulated microglia. We observed secretion of IL‐12, TNF‐α, and NO following stimulation of microglia with LPS. Addition of IL‐10 suppressed TNF‐α, IL‐12, and NO production. Transforming growth factor‐β (TGF‐β) also inhibited TNF‐α and NO but did not affect IL‐12 secretion. IL‐12 secretion became sensitive to TGF‐β inhibition when microglia were cultured in the absence of CSF‐1. In addition to its effect on the response to TGF‐β, CSF‐1 suppressed the response of microglia to LPS. These data suggest that CSF‐1 may contribute to the immunologic ally privileged status of the central nervous system.J. Leukoc. Biol. 60: 502–508; 1996.

ISSN:0741-5400    

DOI:10.1002/jlb.60.4.502

出版商:Wiley    

年代:1996

数据来源: WILEY