摘要:

AbstractReceptors in the nerve growth factor/tumor necrosis factor receptor family are characterized by the presence of cysteine‐rich motifs of ~40 amino acids in the extracellular domain. The ligands are type II transmembrane proteins with β‐strands that form a jelly‐roll β‐sandwich. The receptors recognize soluble or cell‐surface‐bound ligands and mediate diverse cellular responses. Activation of intracellular signals is mediated at least in part by the association of proteins with a RING finger motif or a death domain to the cytoplasmic domains of the receptors. In addition to cell‐membrane‐bound receptors soluble forms have been described for most of the receptors. Activation of intracellular signals not only occurs through ligand binding to the receptors but cross‐linking of at least some members of the ligand family can regulate cell functions.

ISSN:0741-5400    

DOI:10.1002/jlb.60.1.1

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractThrough its action on macrophages, bacterial lipopolysaccharide (LPS) or endotoxin can trigger responses that are protective or injurious to the host. This review examines the effects of LPS on macrophages by following events from the cell surface to the nucleus. The involvement of protein tyrosine kinases, mitogen‐activated protein kinases, protein kinase C, G proteins, protein kinase A, ceramide‐activated protein kinase, and microtubules in this process are reviewed. At the nuclear level, rel, C/EBP, Ets, Egr, fos, and jun family members have been implicated in activation of LPS‐inducible gene expression.

ISSN:0741-5400    

DOI:10.1002/jlb.60.1.8

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractSubcutaneous injection of recombinant human interleukin‐2 (rhuIL‐2) at 102‐104U/mouse induced delayed (48 h) accumulation of mononuclear leukocytes with diffuse granulocytes, including eosinophils. Subcutaneous local infusion of rhuIL‐2 or recombinant murine IL‐2 (102–104U/mouse) via implanted Alzet miniosmotic pumps in mice induced chronic inflammatory lesions characterized by infiltration of large vacuolated mononuclear leukocytes, lymphoid cells, and eosinophil foci; neovascularization, with high endothelial‐like cells, was prominent, exhibiting intravascular trapping and migration of large mononuclear leukocytes. Leukocyte infiltrates comprised T lymphocytes (CD4+; CD8+), B lymphocytes, and macrophages. Control infusions of bovine serum albumin (BSA) induced weak fibrotic lesions with sparse macrophage infiltration and minimal accumulation of lymphocytes; VLA4+and ICAM‐1+leukocyte infiltrates were significantly greater in IL‐2‐induced lesions compared with BSA‐induced lesions. Quantitative image analysis showed significantly increased lesion size in the IL‐2‐induced lesions compared with those induced by BSA infusion. The vascularity of IL‐2‐induced lesions assessed by immunostaining for platelet‐endothelial cell adhesion molecule was increased compared with control, BSA‐induced lesions mainly due to neovascularization. ICAM‐1 and VCAM‐1 expression was significantly enhanced in IL‐2 lesions. No systemic pathological changes were observed following IL‐2 infusion. We conclude that local slow‐release of IL‐2 causes the evolution and maintenance of a specific chronic inflammatory lesion.

ISSN:0741-5400    

DOI:10.1002/jlb.60.1.27

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractThe white blood cell (WBC) elements and the bone marrow myeloid progenitor cell populations were analyzed to ascertain adaptation to microgravity and subsequent readaptation to 1 G in rats flown on the 14‐day Spacelab Life Sciences‐2 (SLS‐2) mission. Bone marrow cells were harvested from one group of rats killed inflight (FD13) and blood was drawn from three other groups at various times. The WBC level was normal on FD14 with the exception of neutrophilia. On FD13, numbers of colony‐forming units‐granulocyte (CFU‐G), CFU‐GM, and CFU‐M from flight animals were decreased compared with ground controls when incubated with recombinant rat interleukin‐3 (rrIL‐3) alone or in combination with recombinant human erythropoietin (rhEpo). On recovery (R + 0), flight rats had decreased numbers of total leukocytes and absolute numbers of lymphocytes and monocytes with elevated neutrophils compared with control rats. They had lower numbers of CD4, CD8, CD2, CD3, and B cells in the peripheral blood but no differences in spleen lymphocytes.

ISSN:0741-5400    

DOI:10.1002/jlb.60.1.37

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractWe have shown that normal C57BL/6J mice are moderately resistant to infection with murine cytomegalovirus (MCMV) and that this resistance is impaired by prior infection with LP‐BM5 MuLV, which causes a disease (MAIDS) similar to early HIV‐induced disease. This study investigates macrophage function in MAIDS+mice challenged with MCMV. MAIDS reduces the influx of cells into the peritoneal cavity seen in normal C57BL/6J mice 6 days after MCMV infection. The infiltrates contained cells that resembled activated macrophages, as they took up colloidal gold, expressed the macrophage marker Mac‐1, had high levels of acid phosphatase activity, and were lymphocytostatic when co‐cultured with activated T cells. MAIDS+mice had a higher percentage of cells able to take up colloidal gold and higher acid phosphatase activity per cell. The cells were also more lymphocytostatic and produced higher levels of interleukin‐1 and tumor necrosis factor‐α on days 4 and 6 after MCMV infection. Hence, MAIDS enhances baseline and induced macrophage activity, but depresses infiltration into the site of inflammation.

ISSN:0741-5400    

DOI:10.1002/jlb.60.1.44

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractImmunotherapy with interleukin‐2 (IL‐2) is limited by severe side effects thought to be mediated by the activation of immune effector cells and the induction of secondary cytokines including tumor necrosis factor‐alpha (TNF‐α) and interferongamma (IFN‐γ). In C3H/HeN mice the primary IL‐2 toxicity is the production of pleural effusion with subsequent respiratory compromise. IL‐10 is a cytokine that has been shown to inhibit the generation of secondary cytokines in vitro and in vivo. In this study, in C3H/HeN mice, we tested the ability of IL‐10 to inhibit IL‐2‐induced mononuclear cell and alveolar macrophage activation and IL‐2‐induced increases in serum TNF‐α and IFN‐γ, all of which may contribute to the generation of toxicity. IL‐10 was ineffective at reducing IL‐2‐induced pleural effusion. However, IL‐10 did inhibit IL‐2‐induced increases in serum TNF‐α, which was accompanied by a decrease in Golgi apparatus and rough endoplasmic reticulum in alveolar macrophages. In addition, ILIO combined with IL‐2 increased mononuclear cell activation, which may limit the ability of IL‐10 to inhibit IL‐2‐induced IFN‐γ production and pulmonary injury.

ISSN:0741-5400    

DOI:10.1002/jlb.60.1.51

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractThe interaction of platelets with neutrophil granulocytes is considered to play an important role in the inflammatory process, and the present study was focused on platelet‐induced modulation of Fcγy receptor‐mediated functions in neutrophils. We found that phagocytosis and the respiratory burst (measured as luminol‐enhanced chemiluminescence), triggered in neutrophils by immunoglobulin G (IgG)‐opsonized yeast particles, were potentiated by platelets and that maximal enhancement was achieved at a physiological neutrophil/platelet ratio of about 1:50 to 1:100. Platelets both increased the intra‐ and extracellular generation of oxygen radicals as well as the release of myeloperoxidase from stimulated neutrophils. The presence of platelets also induced a cortical actin polymerization in neutrophils, which might explain the increased phagocytic capacity. Platelets appear to affect neutrophil function in a contact‐independent manner that most likely involves ATP, indicated by the following: (1) platelet supernatants, but not fixed platelets, affected neutrophil function in the same way as viable platelets; (2) platelets raised the extracellular ATP level four‐ to fivefold; (3) exogenous ATP mimicked the effects of platelets on actin polymerization, phagocytosis, and the respiratory burst in neutrophils; (4) hydrolysis of extracellular ATP with apyrase or blocking of ATP receptors with suramin reversed the platelet‐induced enhancement of neutrophil function. An increased accumulation of extracellular adenosine, induced by inhibiting endogenous adenosine deaminase or adding exogenous adenosine, reversed the effects of platelets. The platelet‐induced potentiation of the respiratory burst was inhibited by the tyrosine kinase inhibitor genistein, suggesting that tyrosine phosphorylation is involved. However, platelets did not significantly affect the Fcγ receptor‐triggered calcium response in neutrophils. In conclusion, we show that platelets, through an ATP‐dependent mechanism, potentiate IgG‐mediated ingestion and production of oxygen metabolites in neutrophils.

ISSN:0741-5400    

DOI:10.1002/jlb.60.1.58

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractHumans subjected to periods of microgravity develop anemia, thrombocytopenia, and abnormalities in red blood cell structure. The causes of these abnormalities are complex and unclear. The in vitro effects of spaceflight on hematopoietic cell proliferation and differentiation were investigated during the space shuttle missions STS‐63 (Discovery) and STS‐69 (Endeavour). CD34+bone marrow progenitor cells were cultured in liquid suspension culture and on hematopoietic supportive stromal cells using hollow‐fiber culture modules. One set of cultures was maintained at microgravity (flight cultures) for the last 8–10 days of culture and a second control was at full gravity (ground control). Over the 11‐ to 13‐test‐day period, ground control culture total cell number increased 41.0‐ to 65.5‐fold but flight culture total cell number increased only 10.1‐ to 17.6‐fold (57–84% decrease). Comparing ground control cultures and microgravity cultures, respectively, for progenitor cell content, myeloid progenitor cell numbers expanded 2.6‐ to 17.5‐fold compared with 0.9‐ to 7.0‐fold and erythroid progenitor cell numbers expanded 2.0‐ to 4.1‐fold in ground control cultures but actually declined at microgravity (>83% reduction). Moreover, microgravity cultures demonstrated accelerated maturation/differentiation toward the macrophage lineage. These data indicate that spaceflight has a direct effect on hematopoietic progenitor cell proliferation and differentiation and that specific aspects of in vitro hematopoiesis, particularly erythropoiesis, involve gravity‐sensitive components.

ISSN:0741-5400    

DOI:10.1002/jlb.60.1.69

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractIn this study, the effects of platelet release products (PRPr), ATP, and ADP on the adhesion of human neutrophils to human umbilical vein endothelial cells (HUVEC) and nylon fibers (NF) are described and the implications of various adhesion molecules are considered. Adhesion of neutrophils to HUVEC and NF was increased by PRPr, ATP, and ADP, while their adhesion‐increasing actions were cancelled or considerably repressed by apyrase treatment. When anti‐CD11a or anti‐CD11b was added to neutrophils with PRPr, ATP, or ADP, the adhesion‐increasing action was cancelled or considerably repressed. On the other hand, anti‐ICAM‐1 and anti‐CD35 had no significant effects on this action. The above results indicated that platelets, through ATP and ADP in PRPr, increased the adhesion of neutrophils to endothelial cells and foreign bodies. Although it was suggested that the adhesion‐increasing action was at least partially based on CD11a and CD11b, ICAM‐1 and CD35 had no part in the enhancement of the adhesion.

ISSN:0741-5400    

DOI:10.1002/jlb.60.1.77

出版商:Wiley    

年代:1996

数据来源: WILEY

摘要:

AbstractInteraction ofCandida albicanswith cells of the macrophage lineage was examined by using heat‐killed (HK) and live yeast cells. Laminarin, an analogue of the cell wall β‐glucans, strongly inhibited HK yeasts adherence to J774 cell line but had no effect on live yeast binding. Phosphopeptidomannan (PPM) fromSaccharomyces cerevisiaehad a limited effect on the binding of both HK and live yeasts but significant inhibition was achieved by the use ofC. albicansPPM. The role of β‐1,2‐oligomannosides was examined with regard to their exclusive presence withinC. albicansPPM. PPM acid labile β‐1,2‐oligomannosides or a synthetic β‐1,2‐mannotetraose, inhibited yeasts binding in a manner comparable to the original PPM. These latter results were confirmed by using mouse peritoneal macrophages, thus suggesting a general role for β‐1,2‐oligomannosides in the adherence of the yeast to the macrophage membrane.

ISSN:0741-5400    

DOI:10.1002/jlb.60.1.81

出版商:Wiley    

年代:1996

数据来源: WILEY