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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine the effects of the atmospheric pollutant formaldehyde on functionally distinct mast cells, peritoneal mast cells (PMC), intestinal mucosal mast cells (IMMC) and mouse bone-marrow-derived mast cells (BMMC) were incubated with various concentrations of formaldehyde. Pretreatment for 30 min with up to 100 micrograms/ml formaldehyde was not cytotoxic to mast cells. Formaldehyde (1-10 micrograms/ml) alone induced low levels of histamine release (< 10%) from IMMC and BMMC. Antigen-induced histamine release was significantly increased in both PMC pretreated with low concentrations of formaldehyde (5-20 micrograms/ml) and BMMC pretreated with 10 micrograms/ml formaldehyde but decreased in PMC pretreated with a higher concentration (100 micrograms/ml) of formaldehyde. By contrast, antigen-induced histamine release was decreased in IMMC pretreated with formaldehyde in a dose-dependent manner. Histamine release stimulated with A23187 was also increased in PMC pretreated with a low concentration (10 micrograms/ml) of formaldehyde but decreased in those pretreated with a higher concentration (100 micrograms/ml) of formaldehyde. Pretreatment with 10 micrograms/ml formaldehyde significantly enhanced beta-hexosaminidase release from PMC stimulated with antigen or A23187. Compared to sham-treated PMC, PMC pretreated with formaldehyde expressed a markedly depressed natural cytotoxicity for the tumor target WEHI-164 (an assay of tumor necrosis factor alpha activity). These results suggest that formaldehyde modifies various mast cell functions through alterations in cellular metabolism. Such effects may be important in respiratory and other diseases associated with formaldehyde exposure.
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PMID:Mast cell response to formaldehyde. 1. Modulation of mediator release. 138 64

Mast cell-associated mediators are generally classified into two groups: the preformed mediators, which are stored in the cells' cytoplasmic granules and are released upon exocytosis, and the newly synthesized mediators, which are not stored but are produced and secreted only after appropriate stimulation of the cell. We now report that tumor necrosis factor alpha (TNF-alpha)/cachectin represents a new type of mast cell-associated mediator, in that IgE-dependent mast cell activation results in the rapid release of preformed stores of the cytokine followed by the synthesis and sustained release of large quantities of newly formed TNF-alpha. We also demonstrate that challenge with specific antigen induces higher levels of TNF-alpha mRNA at skin sites sensitized with IgE in normal mice or mast cell-reconstituted genetically mast cell-deficient WBB6F1-W/W1' mice than at identically treated sites in WBB6F1-W/W1' mice that are devoid of mast cells. These findings identify mast cells as a biologically significant source of TNF-alpha/cachectin during IgE-dependent responses and define a mechanism whereby stimulation of mast cells via the FC epsilon RI can account for both the rapid and sustained release of this cytokine.
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PMID:Release of both preformed and newly synthesized tumor necrosis factor alpha (TNF-alpha)/cachectin by mouse mast cells stimulated via the Fc epsilon RI. A mechanism for the sustained action of mast cell-derived TNF-alpha during IgE-dependent biological responses. 182 7

Histamine and tumor necrosis factor alpha (TNF-alpha) can each contribute to the pathogenesis of allergic reactions and chronic inflammatory diseases. We now report the effect of histamine on gene expression and total cellular synthesis of TNF-alpha. Lipopolysaccharide (LPS)-induced synthesis of TNF-alpha in peripheral blood mononuclear cells (PBMC) from 18 healthy donors was suppressed by histamine concentrations from 10(-6) to 10(-4) M, levels comparable with those measured in tissues after mast cell degranulation. Histamine (10(-5) M) markedly suppressed LPS-induced synthesis of TNF-alpha in both unfractionated PBMC (83% inhibition, p less than 0.001) and monocytes purified by positive selection of LeuM3+ cells (62% inhibition, p less than 0.05). The suppressive effect of histamine on TNF-alpha synthesis did not require the presence of T cells. The histamine-mediated decrease in TNF-alpha synthesis was not affected by indomethacin, nor by diphenhydramine, an H1 receptor antagonist, but was reversed by cimetidine or ranitidine, H2 receptor antagonists, in a dose-dependent manner. Suppression of TNF-alpha synthesis by histamine is likely to be a transcriptional event, since histamine (10(-5) M) reduced TNF-alpha mRNA levels fourfold. These results suggest that histamine release from mast cells may paradoxically limit the extent of inflammatory and immune reactions by suppressing local cytokine synthesis in H2 receptor-bearing cells.
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PMID:Histamine suppresses gene expression and synthesis of tumor necrosis factor alpha via histamine H2 receptors. 205 80

The proliferation of mucosal mast cells (MMC) depends on the presence of interleukin 3 (IL 3) and can be further enhanced by interleukin 4 (IL 4). The supernatant of a TH2 cell clone (ST2/K.9) stimulated by concanavalin A was found to contain a factor, provisionally termed mast cell costimulatory activity (MCA), that substantially enhances the proliferation of MMC promoted by a combination of IL 3 and IL 4. In comparison to other lymphokines MCA is rather resistant to tryptic digestion but is very sensitive to pH values lower than 6.0 and to organic solvents. Chromatographic fractionation of MCA revealed that activity is associated with protein(s) or glycoprotein(s) of 35 to 40 kDa. Partially purified MCA that was functionally free of other T-cell-derived lymphokines did not stimulate mast cell proliferation in the absence of a combination of IL 3 and IL 4. In addition, MCA did not affect the proliferation of mast cells when employed together with either IL 3 or IL 4 alone. Control experiments demonstrated that MCA is identical to neither the T-cell-derived lymphokines IL 2 to IL 6, IL 9, interferon gamma, tumor necrosis factor alpha or beta, or granulocyte-macrophage colony-stimulating factor (CSF), nor to IL 7, granulocyte CSF, macrophage CSF, erythropoietin, leukemia inhibitory factor, or epidermal growth factor (EGF). Finally, experiments using a panel of PPD-reactive TH1- and TH2-like cell lines revealed that MCA is preferentially produced by TH2 cells. These data, especially the relative resistance of MCA to trypsin and the high sensitivity to low pH values and organic solvents, indicate that MCA is distinct from known T-cell-derived lymphokines.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of a T-cell-derived mast cell costimulatory activity (MCA) that acts synergistically with interleukin 3 and interleukin 4 on the growth of murine mast cells. 210 34

To understand better the role of mast cell secretory products in the genesis of inflammation, a system was developed for in vitro degranulation of human mast cells in skin organ cultures. Within 2 hr after morphine sulfate-induced degranulation, endothelial cells lining microvessels adjacent to affected mast cells expressed an activation antigen important for endothelial-leukocyte adhesion. Identical results were obtained when other mast cell secretagogues (anti-IgE, compound 48/80, and calcium ionophore A23187) were used. Induction of this antigen was abrogated by preincubation with cromolyn sodium, an inhibitor of mast cell secretion, and by antiserum to tumor necrosis factor alpha. These findings indicate that degranulation of mast cells activates dermal endothelium through tumor necrosis factor-dependent mechanisms. This event may be critical to the elicitation phase of cutaneous inflammation.
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PMID:Degranulation of human mast cells induces an endothelial antigen central to leukocyte adhesion. 247 33

Decentralization or ganglionectomy of the superior cervical ganglia (SCG) reduces pulmonary inflammation, as well as chemotaxis and activation of circulating neutrophils. However, the protective effect of decentralization was abolished when combined with removal of the submandibular glands (sialadenectomy) in the same animals. Thus, it has been postulated that the submandibular glands (SMG) release an anti-inflammatory factor(s) that is controlled by cervical sympathetic nerves. Decentralization of SCG did not modify in vitro histamine release or in vivo levels of rat mast cell protease II, but it reduced mast cell (MC)-mediated tumor necrosis factor alpha (TNF alpha)-dependent cytotoxicity. Combined decentralization/sialadenectomy abrogated the inhibition of MC cytotoxic activity, as we have shown previously for pulmonary inflammation and neutrophil functions. However, sialadenectomy alone inhibited MC-mediated TNF alpha-dependent cytotoxicity, an observation which suggests that SMG produce a factor(s) that can potentiate MC cytotoxic activity. Studies of the effects of SMG-derived factors, such as epidermal growth factor, nerve growth factor, and transforming growth factor beta (TGF beta), showed that only pretreatment of MCs with TGF beta 10(-8) g/ml inhibited MC-mediated TNF alpha-dependent cytotoxicity. Thus, the modulation of MC-mediated TNF alpha-dependent cytotoxicity by cervical sympathetic innervation and SMG is complex and distinct from the modulation of pulmonary inflammation and neutrophil functions identified previously.
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PMID:Decentralization of the superior cervical ganglia inhibits mast cell mediated TNF alpha-dependent cytotoxicity. 1. Potential role of salivary glands. 750 95

The expression of tumor necrosis factor alpha (TNF) protein in mouse myometrial cells on each day of the estrous cycle and after ovariectomy, with and without replacement of estradiol (E2), progesterone (P4), or E2 + P4, was investigated. TNF protein was assessed by immunocytochemistry. In addition, the numbers of mast cells and the numbers of TNF-containing mast cells were determined under each condition. The total number of mast cells fluctuated during the estrous cycle; and at each stage, essentially 100% of the mast cells exhibited TNF immunoreactivity. In contrast, after ovariectomy and after ovariectomy with E2 replacement, only approximately 50% of the mast cells contained immunoreactive TNF. P4 treatment resulted in further decline in mast cell TNF whereby after 24 h of P4, only 3% of the mast cells were TNF-positive and by 72 h of treatment, no TNF-positive mast cells could be detected E2 and P4 in combination increased the total number of mast cells, and in a pattern reminiscent of normal cycling myometrium, over 90% of the mast cells exhibited TNF immunoreactivity after 24 h of treatment. TNF protein was detectable in muscle cells throughout the estrous cycle, with weak immunostaining observed on proestrus and more intense immunostaining on estrus, diestrus-I, and diestrus-II. After ovariectomy, only light immunostaining was observed in the muscle cells. Immunoreactive TNF was detected in muscle cells after each type of steroid treatment. E2 and E2 + P4 treatments resulted in a biphasic pattern of immunoreactive TNF expression.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myometrial tumor necrosis factor alpha: cellular localization and regulation by estradiol and progesterone in the mouse. 775 46

Chronic allergic diseases and other disorders associated with mast cell activation can also be associated with tissue fibrosis, but a direct link between mast cell mediator release and fibroblast collagen gene expression has not been established. Using in situ hybridization, we show that the elicitation of an IgE-dependent passive cutaneous anaphylaxis (PCA) reaction in mice results in a transient, but marked augmentation of steady state levels of type alpha-1 (I) collagen mRNA in the dermis. While peak levels of collagen mRNA expression in the skin are observed 16-24 h after mast cell activation, substantial numbers of dermal cells are strongly positive for collagen mRNA at 1 and 2 h after antigen challenge, before circulating inflammatory cells are recruited into the tissues. Furthermore, experiments in mast cell-reconstituted or genetically mast cell-deficient WBB6F1-W/Wv mice demonstrate that the increased expression of collagen mRNA at sites of PCA reactions is entirely mast cell dependent. In vitro studies show that the supernatants of mouse serosal mast cells activated via the Fc epsilon RI markedly increase type alpha-1 (I) collagen mRNA levels in mouse embryonic skin fibroblasts, and also upregulate collagen secretion by these cells. The ability of mast cell supernatants to induce increased steady state levels of collagen mRNA in mouse skin fibroblasts is markedly diminished by absorption with antibodies specific for either of two mast cell-derived cytokines, transforming growth factor beta (TGF-beta 1) or tumor necrosis factor alpha (TNF-alpha), and is eliminated entirely by absorption with antibodies against both cytokines. Taken together, these findings demonstrate that IgE-dependent mouse mast cell activation can induce a transient and marked increase in steady state levels of type alpha-1 (I) collagen mRNA in dermal fibroblasts and that mast cell-derived TGF-beta 1 and TNF-alpha importantly contribute to this effect.
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PMID:Promotion of mouse fibroblast collagen gene expression by mast cells stimulated via the Fc epsilon RI. Role for mast cell-derived transforming growth factor beta and tumor necrosis factor alpha. 796 80

Rat mast cell lines (hybrid rat mast cells, HRMC, and rat cultured mast cells, RCMC) and mast cells from the rat body cavity were used to test the hypothesis that IFN-alpha/beta and IFN-gamma inhibit tumor necrosis factor alpha (TNF-alpha)-mediated cytotoxicity by depressing the steady-state levels of mRNA for TNF-alpha. In vitro treatment of mast cells with IFN-gamma and IFN-alpha/beta depressed mRNA levels. By contrast, IFN pretreatment of mast cell lines induced an increase in levels of mRNA for the IFN-inducible gene, 2'5'-oligoadenylate synthetase and also for high-affinity IgE-receptor-alpha. The IFN-mediated regulation of mast cells may be an important mechanism in the control of inflammatory pathways characterized by Th1- and Th2-type responses.
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PMID:Regulation of mRNA levels of TNF-alpha and the alpha chain of the high-affinity receptor for IgE in mast cells by IFN-gamma and alpha/beta. 864 88

Mast cells are well known effector cells not only in allergic but also in diverse acute and chronic inflammatory diseases. We have shown previously that these cells produce a broad spectrum of cytokines which might contribute to mast cell-dependent pathology. In the present study, we have investigated the influence of four potent glucocorticoids, methylprednisolone-aceponate, methylprednisolone-17-propionate, prednicarbate, and betametasone valerate (10(-5) M-10(-9) M), on the IL-1 beta, IL-3, IL-8, and tumor necrosis factor alpha secretion of the HMC-1 mast cell line as measured by ELISA. All four glucocorticoids caused a comparable dose- and time-dependent inhibition of cytokine release from HMC-1 cells stimulated for 24 h with phorbol 12-myristate 13-acetate 25 ng/ml and calcium ionophore 2 x 10(-7) M. These results shed further light on the mechanisms involved in antiinflammatory effects of glucocorticoids in allergic inflammation.
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PMID:Modulation of in vitro cytokine release from human leukemic mast cells (HMC-1) by glucocorticoids. 872 2


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