Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vitro production of histamine releasing factor (HRF) by lymphoid cells of rats, both normal and infected with Nippostrongylus brasiliensis, has been studied. Spleen cells and thymocytes were cultured either alone or in the presence of mitogen (PHA, 10 and 50 micrograms/ml) and the dialysed cell-free supernatants were tested for histamine releasing activity on rat peritoneal and pleural mast cell in vitro. We found that spleen cells and thymocytes of normal rats stimulated with PHA in 24 h cultures generated a factor which released histamine and 5-hydroxytryptamine from mast cells, and this ability was potentiated following N. brasiliensis infection of rats - lymphoid cells donors. Pleural mast cells were more sensitive to the action of HRF than peritoneal cells. Rat HRF had an apparent m.w. of 50,000 to 70,000 daltons as determined by gel chromatography and was a heat stable protein inducing histamine release from homologous mast cells in a very rapid (complete in 1-2 min at 37 degrees C), dose and temperature dependent secretory process.
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PMID:Rat lymphoid cell--derived histamine and 5-hydroxytryptamine releasing factor. 128 Apr 98

Recent attention has focused on the T helper type 2 (Th2) lymphocyte as a source of interleukin 4 (IL-4) in allergic disease. However, Th2 cells themselves require a pulse of IL-4 to initiate this synthesis. Here we provide immunohistochemical evidence of IL-4 localization to human mast cells of the skin and respiratory tract, and demonstrate that immunoglobulin E-dependent stimulation of purified human lung mast cells leads to the rapid release of IL-4 into the extracellular environment. We propose that mast cell activation in an allergic response provides a rapid and local pulse of IL-4 into the local environment essential for the triggering of T lymphocytes into sustained IL-4 production and to initiate inflammatory cell accumulation and activation.
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PMID:Interleukin 4 is localized to and released by human mast cells. 140 83

Histamine releasing factors (HRF) are a group of cytokines that cause degranulation of basophils and mast cells. Recently we have described a histamine release inhibitory factor (HRIF) that inhibits HRF-induced histamine release from basophils and mast cells. The objective of this study was to investigate the presence of these cytokines in bronchoalveolar lavage (BAL) fluid from normal subjects. We found that BAL fluids from 12 to 17 volunteers contained a dialyzable (molecular weight cutoff 3500) factor that inhibited basophil histamine release by HRF, anti-IgE, concanavalin A, and N-formyl-methionyl-leucyl-phenylalanine (FMLP). In addition, BAL fluids from 83% of the tested donors contained a nondialyzable inhibitor that blocked HRF-induced histamine release from basophils. The molecular weight of this inhibitor was estimated to be 20 to 30 and 8 to 10 kD by Sephadex G-50 chromatography and TSK 2000 size-exclusion HPLC. None of the unconcentrated BAL fluids showed any HRF activity on initial screening using basophils from allergic subjects. However, when the BAL fluids were concentrated, all BAL samples that were tested (N = 10) demonstrated significant HRF activity. The molecular weight of BAL HRF has been estimated to be in the range of 15 to 25 kD by size-exclusion HPLC, similar to the HRF synthesized by mononuclear cells. Thus we have demonstrated the presence of both HRF and HRIF in the BAL fluids. We speculate that these cytokines may be involved in the local regulation of basophil and mast cell activation.
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PMID:Detection of histamine release inhibitory factor- and histamine releasing factor-like activities in bronchoalveolar lavage fluids. 168 75

As elevated bronchoalveolar lavage (BAL) fluid histamine levels are noted in patients with pulmonary fibrosis (PF), we assayed BAL fluid from 16 patients with PF for the presence of a histamine releasing factor (HRF). HRF activity was assayed by measuring release of the preformed mast cell-derived mediators, histamine, or beta-hexosaminidase (beta-hex) from a purified population of IL-3 dependent mouse bone marrow derived mast cells (MBMMC) or human blood basophils. Mean BAL cell free histamine levels in the patients with PF was 1226 +/- 1349 pg/ml, whereas BAL histamine levels in a comparison group of six non-PF patients was 118 +/- 60 pg/ml. HRF was significantly elevated in BAL fluid of patients with PF (mean beta-hex release 24.5 +/- 12.9%; range 6.8 to 52.4%) compared to the non-PF group of patients (mean beta-hex release 7.9 +/- 7.7%; range 1.8 to 20.7%). The PF HRF not only degranulated MBMMC, but also induced the generation of the arachidonic acid metabolite leukotriene C4 from MBMMC (24.6 +/- 4.2 ng leukotriene C4/10(6) MBMMC). The PF HRF did not appear to be a cytokine previously identified in BAL fluid of patients with PF (i.e., platelet derived growth factor or insulin growth factor-1) or a human cytokine able to degranulate human basophils (i.e., IL-1, or granulocyte-macrophage-CSF) as these recombinant human cytokines did not induce MBMMC beta-hex release. Physicochemical characterization of the HRF revealed that it was relatively heat stable, pronase sensitive and on Sephadex G-75 and G-200 column chromatography had an apparent molecular mass of 30 to 50 kDa. The ability of PF BAL to induce beta-hex release from MBMMC was not dependent on IgE as unsensitized or lactic acid treated MBMMC release similar amounts of beta-hex compared to MBMMC sensitized with IgE. Thus, BAL fluid of patients with PF contains an HRF that induces beta-hex release from MBMMC via an IgE-independent mechanism. The presence of the HRF could explain elevated BAL histamine levels in patients with PF.
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PMID:Mast cells and pulmonary fibrosis. Identification of a histamine releasing factor in bronchoalveolar lavage fluid. 169 11

The aim of our work was to investigate the effect of histamine releasing factor (HRF), produced in vitro by lymphocytes obtained from atopic and non-atopic asthmatics, on mast cells of various species (mouse - peritoneal mast cells, hamster and rat - peritoneal and pleural mast cells, guinea-pig - mesenteric and pulmonary mast cells). We found that human HRF is able to release histamine from the examined mast cell populations in a dose-dependent fashion. Mast cells from various species differed in their susceptibility to the action of HRF; rat pleural and guinea-pig mesenteric and pulmonary mast cells were the most susceptible, while mouse and hamster peritoneal mast cells - the least susceptible. The presence of 50% D2O in the medium significantly increased HRF-induced histamine release from rat mast cells, while the addition of phosphatidylserine did not change it. HRF-induced histamine release from guinea-pig mesenteric mast cells was not related to sensitization of these cells. We also compared histamine release from guinea-pig pulmonary and mesenteric mast cells induced by human HRF produced in vitro by lymphocytes obtained from atopic and non-atopic asthmatics. We have found that supernatant from atopic asthmatics lymphocyte cultures released significantly more histamine than supernatant from non-atopic asthmatics lymphocyte cultures. Our studies give evidence that human HRF acts across the species barrier and induces histamine release from mast cells of various species. The mechanism of HRF action on mast cells seems to be different from that of allergen.
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PMID:Histamine release from mast cells of various species induced by histamine releasing factor from human lymphocytes. 244 80

Previous studies have demonstrated that grain dust can stimulate lymphocyte proliferation and the production of interleukin-1 by macrophages. This study was undertaken to investigate whether grain dust could stimulate the production of histamine-releasing factor (HRF) by guinea pig spleen cells. We also studied the direct action of grain dust on guinea pig lung mast cells and basophils. Plastic nonadherent cells from immunized animals were cultured for 24 hours in the presence of grain dust or lipopolysaccharide, and the cell-free supernatants were assayed for HRF activity in the mast cell and basophil histamine release test. Lung mast cells were isolated by enzymatic digestion and discontinuous Percoll gradient centrifugation. It has been demonstrated that grain dust stimulated the production of HRF by spleen cells from the immunized animals but not from the control animals. Stimulation of spleen cells with lipopolysaccharide did not enhance the HRF production. Gel chromatography of grain dust-stimulated supernatant revealed that HRF has a molecular weight in the range of 50 to 70 kd and 5 to 8 kd. We also found that grain dust directly released significant amount of histamine from both mast cells and basophils. The results of this study suggest that grain dust contains some potent active substances that can activate lymphocytes, mast cells, and basophils.
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PMID:Activation of guinea pig lymphocytes and mast cells by grain-dust extract. 245 Jan 15

In our previous studies we reported that lymphocytes from patients with asthma spontaneously produce histamine-releasing factor (HRF) in vitro. In an effort to examine whether spontaneous HRF production (SpHRF) by lymphocytes from patients with asthma is related to the state of bronchial hyperreactivity (BHR), 20 patients with mild to severe asthma were studied. Peripheral blood lymphocytes were cultured alone in a serum-free medium for 24 hours, and culture supernatant was assayed for HRF activity in two separate histamine-release tests with autologous basophils and normal basophils from known healthy donors. BHR was measured as bronchial reactivity to inhaled histamine and was expressed as a provocation concentration of histamine required to induce a 20% fall in FEV1 (PC20). The result of this study demonstrated that lymphocyte supernatant from all patients with asthma released significant amount of histamine from both autologous and normal basophils. Very high histamine release was usually induced by lymphocyte supernatant from severely ill patients who had PC20 less than 2 mg/ml. Statistical analysis demonstrated that the magnitude of the SpHRF significantly correlated (r = -0.86; p less than 0.001) with PC20. Since mast cell- and basophil-derived mediators have been implicated in the pathogenesis of BHR, high correlation between PC20 and SpHRF by lymphocytes suggests that the latter may contribute to the development of BHR. Further studies are required to disclose the exact relationship between SpHRF and BHR.
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PMID:The magnitude of the spontaneous production of histamine-releasing factor (HRF) by lymphocytes in vitro correlates with the state of bronchial hyperreactivity in patients with asthma. 380 41

We have previously reported that monocyte chemoattractant protein-1 (MCP-1) is the most potent histamine-releasing factor (HRF) for basophils. Macrophage inflammatory protein-1 alpha (MIP-1 alpha) has modest histamine-releasing activity. The objective of this study was to investigate whether MCP-1 and MIP-1 alpha would activate mast cells in vivo and induce a cutaneous inflammatory reaction in mice. To this goal, mouse hind footpads were separately injected with 20 microliters of human recombinant MCP-1 or MIP-1 alpha (10(-7) M). Diluent was used as a control in the second footpad. The footpad-swelling response was measured at 30 min, 1 h, and then hourly for 6 h. Both MCP-1 (2.72 +/- 0.2 vs 2.1 +/- 0.03 mm for diluent, n = 8, p < 0.02) and MIP-1 alpha (3.0 +/- 0.1 vs 2.1 +/- 0.03 mm for diluent, n = 8, p < 0.02) induced an immediate swelling reaction. The immediate reaction was followed by a sustained late reaction that peaked within 1 h and lasted for more than 6 h. Histologic examination of the footpads, obtained at hour 2, revealed that MCP-1 caused mild mononuclear cell infiltrates, moderate degranulation of mast cells, and soft tissue swelling. In contrast, MIP-1 alpha induced a severe inflammatory reaction that consisted of neutrophils, mononuclear cells, and degranulated mast cells. Electron microscope examination of the tissue revealed features of extensive mast cell degranulation by MIP-1 alpha and to a lesser extent by MCP-1. Thus, we conclude that mast cells are activated on injection of MCP-1, whereas degranulation of mast cells and recruitment of leukocytes contribute to the footpad reaction induced with MIP-1 alpha.
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PMID:Macrophage inflammatory protein-1 alpha and monocyte chemoattractant peptide-1 elicit immediate and late cutaneous reactions and activate murine mast cells in vivo. 830 Nov 33

Histamine-releasing factor (HRF) consists of a group of cytokines that can cause basophil/mast cell to release histamine, however, the composition of HRF still remains undefined. This study was designed to measure the concentrations of chemokines in asthmatic children receiving immunotherapy. Peripheral blood mononuclear cells culture supernatants were obtained from six asthmatic children before and four, eight months after immunotherapy (IT). The levels of monocyte chemotactic and activating factor (MCAF), macrophage inflammatory protein-1a (MIP-1a), regulated on activation normal T-cell expressed and secreted (RANTES) and interleukin-8 (IL-8) spontaneously and after stimulation with PHA and mite allergen in the supernatants. The data showed: 1) The levels of MCAF and MIP-1a increased four months, and decreased eight months, after IT; 2) By contrast, the level of RANTE increased after IT; 3) The level of IL-8 also tended to increase after IT. Abnormal chemokine production may contribute to the pathogenesis of bronchial asthma and restoration of normal chemokine production may be used to partially explain the clinical efficacy of immunotherapy.
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PMID:Change of chemokines during immunotherapy in asthmatic children. 894 25

Toxins A and B from Clostridium difficile are the main cause of antibiotic-associated diarrhea and pseudomembranous colitis. They cause fluid accumulation, necrosis, and a strong inflammatory response when inoculated in intestinal loops. Since mast cells are a rich source of inflammatory mediators, abundant in the gut, and known to be involved in C. difficile-induced enteritis, we studied the in vitro effect of toxin A on isolated mast cells. Normal rats sensitized by infection with Nippostrongilus brasiliensis were used to isolate peritoneal mast cells (PMC). PMC from naive rats were stimulated with calcium ionophore A23187 as a model of antigen-independent activation, and PMC from sensitized rats were stimulated with N. brasiliensis antigens to study immunoglobulin E-dependent mast cell activation. After 4 h, toxin A did not induce release of nitric oxide or histamine in naive PMC. However, 10 ng of toxin per ml caused a significant release of tumor necrosis factor alpha (TNF-alpha). In contrast, 1 microg of toxin per ml inhibited antigen or A23187-induced histamine release by PMC. Toxin A at 1 microg/ml for 4 h caused disruption of actin which aggregated in the cytoplasm and around the nucleus. After 24 h, chromatin condensation, cytoplasmic blebbing, and apoptotic-like vesicles were observed; DNA fragmentation was documented also. These results suggest that mast cells may participate in the initial inflammatory response to C. difficile infection by releasing TNF-alpha upon interaction with toxin A. However, longer exposure to toxin A affects the release of inflammatory mediators, perhaps because of the alteration of the cytoskeleton and induction of apoptosis. The impaired functions and survival of mast cells by C. difficile toxin A could hamper the capacity of these cells to counteract the infection, thus prolonging the pathogenic effects of C. difficile toxins.
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PMID:Effects of toxin A from Clostridium difficile on mast cell activation and survival. 959 44


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