摘要:

AbstractThe effects of the stable analogue of TxA2, U46619, on polymorphonuclear leukocyte (PMN) function were investigated. U46619, at micromolar concentrations, inhibited fMLP‐stimulated aggregation,β‐glucuronidase release, and superoxide production. fMLP‐induced LTB4synthesis was also inhibited. U46619 did not modify intracellular Ca2+increase induced by fMLP in Fura‐2‐loaded PMN, suggesting that early events of cell activation were not involved. In fact, U46619 also inhibited aggregation,β‐glucuronidase release, superoxide anion and LTB4production induced by the calcium ionophore A23187. By comparison with the specific 5‐lipoxygenase inhibitor, L‐663,536, which prevented LTB4synthesis without affecting degranulation, we excluded the impairment of PMN function by U46619 as a consequence of the reduction of this endogenous agonist. TLC separation of lipid extracts from [3H]‐AA‐loaded PMN, stimulated by A23187, showed significant reduction of the radioactivity associated with authentic free AA, suggesting that U46619 could interfere with mechanisms regulating AA release from membrane phospholipids. This suggestion is also supported by the observation that manoalide, a standard inhibitor of phospholipase A2, similarly to U46619, inhibitsβ‐glucuronidase release from stimulated PMN. Prostaglandin endoperoxides, produced by cells participating in inflammatory reactions, might therefore play a role in modulating PMN activities.J. Leukoc. Biol.57: 72–79; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.72

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractThioglycolate‐elicited murine macrophages from genetically susceptible A/J mice activated with lipopolysaccharide (LPS) and infected withLegionella pneumophilain vitro evince marked inhibition of intracellular growth of this bacterium. The mechanism of inhibition by LPS‐activated macrophages in terms of replication of this intracellular pathogen is unclear. LPS activation of murine macrophages induced a downshift in transferrin receptor (TfR) expression and reduction in cellular iron content, and this was correlated with augmented intracellular growth ofLegionellain the cells. When LPS‐stimulated macrophages were first saturated with iron, partial reversion ofL. pneumophilagrowth restriction was observed. However, an excess of exogenous L‐tryptophan (Trp) did not reverse this growth inhibition, nor did supplementation of the macrophage culture medium with both iron and Trp. The antilegionella activity of the macrophages induced by LPS activation was independent of reactive oxygen intermediates (ROI), since the scavengers catalase, superoxide dismutase, mannitol, and thiourea had no effect on growth restriction. Likewise, notwithstanding the ability of LPS‐activated macrophages to synthesize reactive nitrogen intermediates (RNI), which was inhibited by l‐arginine analogs (NG‐monomethyl‐l‐arginine and l‐aminoguanidine), as well as by incubation in arginine‐free medium, their ability to inhibit the intracellular replication ofL. pneumophilawas not affected. Thus, we conclude that LPS‐activated macrophages inhibit the intracellular growth ofL. pneumophilapartially by iron‐dependent, Trp‐independent, and ROI‐ and RNI‐independent mechanisms. We also suggest that additional unknown mechanisms are involved, since complete reversion was not obtained.J. Leukoc. Biol.57: 80–87; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.80

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractCultured natural killer (NK) cells derived from CD3‐CD56+high‐density small lymphocytes (HDLs) exhibit similar morphology and high levels of non‐major histocompatibility complex‐restricted (NK) cytotoxicity equivalent to those of cultured NK cells from CD3‐CD56+low‐density large granular lymphocytes (LGLs). To examine the similarities and differences between NK cells from HDLs and NK cells from LGLs, we investigated the expression of three distinct members of the granule serine protease (granzyme) family within cultured CD3‐CD56+LGLs and HDLs. CD3‐subpopulations of nonadherent peripheral blood mononuclear cells, LGLs (density1.063 g/ml) were stimulated to proliferate in culture. The cultured cells from each population were entirely CD3‐CD56+and were indistinguishable in terms of their increased granularity and size once activated. All cultured CD3‐CD56+LGLs and HDLs displayed cytolytic activity against K562 and immunoglobulin‐coated P815. Western analysis detected perforin in both cultured LGL and HDL populations. Cultured HDLs and LGLs both expressed BLT‐esterase activity and human granzyme A mRNA. Granzyme B mRNA and protein and Asp‐ase activity were detected in unstimulated and cultured LGLs and cultured HDLs. By contrast, unstimulated HDLs did not express significant levels of granzyme B. High levels of Hu‐Met‐1 granzyme mRNA and Met‐ase activity were detected only in cultured LGLs. Thus, despite the development of large granular morphology during proliferation, interleukin‐2 cultured CD3‐CD56+HDLs display a different pattern of granzyme expression from CD3‐CD56+LGLs. These data also further suggest an unusually restricted expression of the Hu‐Met‐1 granzyme in LGLs.J. Leukoc. Biol. 57: 88–93; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.88

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractA new class of low‐molecular‐weight cysteine‐rich regulatory growth factors, designated granulins, has been isolated from hematopoietic tissues of a teleost fish (Cyprinus carpio) and structurally characterized. Granulin‐1, the predominant form found in carp spleen, was used to raise polyclonal antibodies in rabbits and to establish a radioimmunoassay. This permitted preliminary tissue distribution studies of granulin‐1 to be undertaken in carp (Cyprinus carpio) and goldfish (Carassius auratus). Granulin‐1 immunoreactivity was found in the melanomacrophage centers of the spleen and head kidney. Carp tissues anatomically involved in the first line of defense against infection, including skin, gills, gut, and also heart, showed intense granulin‐1 immunoreactive staining within presumptive macrophage cells. Granulin‐1 immunoreactive macrophages prepared from goldfish spleen and head kidney adhered to glass slides, actively phagocytosed carbon particles, and contained granulin‐1 immunoreactivity as well as abundant endogenous peroxidase activity. This study demonstrates that granulin‐1 is synthesized and stored in macrophages/monocytes of spleen, head kidney, and peripheral tissues of teleost fish.J. Lcukoc. Biol.57: 94–100; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.94

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractSamples of alveolar macrophages (AM) obtained by bronchoalveolar lavage from patients with either paracoccidioidomycosis, silicosis, sarcoidosis, or allergic alveolitis were investigated by electron microscopy and immunocytochemistry to compare cellular ultrastructure and expression of MHC‐II antigens in the AM cell surface. All samples of AM obtained from patients with these pathologies showed heterogeneous structural features. Although, this morphological diversity is also present in AM of healthy donors, our observations seem to indicate that in the diseases studied this morphofunctional diversity is associated with additional ultrastructural characteristics inherent to each disease. In paracoccidioidomycosis the proportion of vacuolated macrophages is significantly lower than in other diseases; this might indicate that in paracoccidioidomycosis the proportion of activated AM is smaller. We observed significant differences in the expression of MHC‐II antigens. Silicosis, sarcoidosis, and allergic alveolitis do not differ significantly in the quantity of immunolabeled AM or in the distribution of the label. The percentage of AM from paracoccidioidomycosis that exhibit the MHC‐II molecule is very low with poor immunolabeling. In this disease the low expression of the MHC‐II molecule could be related to a decrease of the antigen presenting function by AM.J. Leukoc. Biol.57: 101–109; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.101

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractThe ability of substance P (SP) to regulate peak benzyl‐penicilloyl (BPO)‐specific IgE antibody‐forming cell (AFC) responses in vivo and the ability of SP and other neuropeptides to regulate BPO‐specific memory IgE AFC responses induced in vitro was determined. SP injected subcutaneously into BPO‐keyhole limpet hemocyanin (BPO‐KLH)‐sensitized mice at the time of peak IgE responses suppressed these responses within 48 h (>90%). The suppression obtained was IgE isotype‐specific, dose‐dependent, and transient. When spleen cells from immunized mice were cultured for 5 days with BPO‐KLH, peak memory IgE AFC responses were induced in vitro. Inclusion of either SP or vasoactive intestinal peptide (VIP), but not neurotensin, serotonin, somatostatin, or gastrin, in cultures suppressed these responses in isotype‐specific, dose‐dependent fashion (70%). SP‐, but not VIP‐mediated suppression of IgE responses was abrogated by inclusion of anti‐IFNγ in culture.J. Leukoc. Biol.57: 110–115; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.110

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractLymphocyte migration from the blood to sites of tissue injury is mediated, in part, through the interaction of these cells with endothelial cells lining the vessel walls. The ability of endothelial cells to produce nitric oxide may be important in this process. We found that the addition of the nonspecific lymphocyte activators lipopolysaccharide (LPS) or concanavalin A (Con A) to rat hepatic endothelial cell cultures from control or endotoxemic rats markedly enhanced the ability of these cells to produce nitric oxide. In contrast, wheat germ agglutinin (WGA) and phytohemagglutinin (PHA) had no effect on nitric oxide release. Coculture of endothelial cells with lymphocyte‐rich preparations of rat thymocytes or splenocytes stimulated endothelial cell nitric oxide production. This response was enhanced by LPS or Con A and to a lesser extent by WGA or PHA. In contrast to endothelial cells, thymocytes and splenocytes did not produce nitric oxide either in the presence or absence of lymphocyte mitogens. Increased production of nitric oxide by endothelial cells in response to lymphocytes and lymphocyte mitogens was due, at least in part, to increased expression of protein for an inducible form of nitric oxide synthase, as measured by Western blotting. Stimulation of endothelial cell nitric oxide production by thymocytes and splenocytes was inheritable by the specific nitric oxide synthase inhibitorNG‐monomethyl‐L‐arginine and dependent on cell‐cell contact. Thus, nitric oxide production by endothelial cells was reduced when the lymphocytes were physically separated from the endothelial cells using cell culture inserts. We hypothesize that nitric oxide released by endothelial cells increases vascular permeability, thereby allowing the extravasation of lymphocytes into the surrounding tissue, a process that may be important in inflammation, tissue injury, and/or wound healing.J. Leukoc. Biol. 57: 116–121; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.116

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractUnfractionated spleen cells from C3H mice infected a few weeks before withMycobacterium lepraemuriumdeveloped a suppressor activity after overnight culture. This requires contact of plastic adherent cells with nonadherent cells distinct from T, B, or natural killer cells. The present study demonstrates that anti‐interferon‐γ (IFN‐γ) monoclonal antibody and indomethacin totally abrogate the expression, although not the induction, of this activity. Furthermore, culture‐induced suppressor cells selectively inhibit T lymphocyte proliferation, probably by altering the generation of interleukin‐2 (IL‐2) responsiveness through reduction of the affinity and density of high‐affinity IL‐2 receptors on activated cells. These and other previously determined properties of culture‐induced suppressor cells, similar to those of adherent suppressor cells detected in freshly harvested spleen cells at a later stage ofM. lepraemuriuminfection, suggest a common precursor. If so, the present observations should help in defining a strategy to prevent the impairment of cell‐mediated immunity in infected mice.J. Leukoc. Biol.57: 122–128; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.122

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractAminopeptidase (APN) was found to degrade interleukin‐8 (IL‐8) and inactivate its chemotactic activity. The chemotactic activity of IL‐8 was decreased by APN or neutrophil plasma membranes dose‐ and time‐dependently. The chemotactic activity was not inactivated in the presence of bestatin or WM15 monoclonal antibody. The expression of IL‐8 was measured by flow cytometry. On lipopolysaccharide (LPS) stimulation, IL‐8 expression increased for 60 min and then decreased markedly. In contrast, on treatment with LPS and bestatin, the expression of IL‐8 increased continuously for at least 120 min. These results suggest that the expression and release of IL‐8 from phagocytic cells are regulated by the proteolytic effect of APN on IL‐8.J. Leukoc. Biol.57: 129–134; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.129

出版商:Wiley    

年代:1995

数据来源: WILEY

摘要:

AbstractAbuse of nitrite inhalants is common among male homosexuals and a history of abuse has been correlated with seropositivity to HIV and with the incidence of Kaposi's sarcoma among AIDS patients. The present study shows that inhalation exposure of mice to 900 ppm isobutyl nitrite for 45 min/day for 14 days compromised macrophage tumoricidal activity by up to 40% and it remained compromised for at least 7 days after terminating exposures. The inhalation exposures did not affect tumor cell binding but did inhibit inducible nitric oxide (NO•). The NO•synthase inhibitorNG‐methyl‐l‐arginine totally inhibited both NO•production and cytotoxicity, suggesting that reductions in NO•due to inhalant exposure may be responsible for the reduced cytotoxic activity. Exposure to the inhalant increased constitutive production of tumor necrosis factor‐α(TNF‐α). TNF‐αhas been reported to stimulate the replication of HIV and the proliferation of Kaposi's sarcoma cells in vitro.J. Leukoc. Biol.57: 135–140; 1995.

ISSN:0741-5400    

DOI:10.1002/jlb.57.1.135

出版商:Wiley    

年代:1995

数据来源: WILEY