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

Mast cell growth factor (MGF), a molecule that serves as a ligand for the receptor tyrosine kinase c-kit, is important in mast cell differentiation, migration, and activation. Previous studies of paraffin-embedded human skin using antibody to murine MGF and reverse transcription-polymerase chain reaction have demonstrated MGF protein and mRNA expression in keratinocytes and isolated dermal cells. We utilized a monoclonal antibody to human MGF to further define patterns of immunoreactivity in frozen specimens of neonatal and adult skin from normal individuals and from patients with urticaria pigmentosa. In addition to keratinocytes and isolated dermal cells in normal and urticaria pigmentosa skin, MGF was detected in cells lining superficial and mid-dermal vessels. Co-expression of MGF and the vascular antigen CD31, and immunoelectron microscopy, identified MGF-positive cells as endothelial cells. Patterns of endothelial MGF expression were not influenced by mast cell degranulation and endothelial E-selectin induction in vitro. By ultrastructure, unfixed specimens demonstrated MGF expression both within the endothelial cytoplasm and in association with lumenal, but not ablumenal, surfaces. Specimens fixed with Nakane's solution had diminished endothelial cytoplasmic MGF reactivity, but lumenal expression was maintained, suggesting persistence of a membrane-associated reactivity. MGF mRNA was also detected in cultured dermal microvascular endothelial cells using reverse transcription-polymerase chain reaction. These data establish human dermal endothelial cells as sites of MGF production and expression in human skin. Mast cell precursors must home to skin via vascular channels and differentiate in the immediate perivascular space. Thus, endothelial MGF may be an important determinant of adhesion and differentiation of mast cell progenitors expressing receptors for MGF.
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PMID:Human dermal endothelial cells express membrane-associated mast cell growth factor. 752 42

Mast cells are granule-containing secretory cells which are distributed preferentially about the microvascular bed in oral mucosa. This work examined the contribution of mast cell mediators to inflammation in the oral cavity. Mast cells in oral tissues expressed the serine proteases, tryptase and chymase, with a minor subpopulation being chymase-negative. Mast cells contained the cytokine tumour necrosis factor-alpha (TNF) in their granules. Degranulation of mast cells was a consistent feature of inflammatory lesions (lichen planus, gingivitis, pulpitis, periapical inflammation). In lichen planus, intracellular stores of TNF were depleted, and expression of mRNA for TNF was upregulated, indicating ongoing production and release of the cytokine. The density of mast cells in tissue compartments was related to the level of expression of E-selectin, an endothelial adhesion molecule which is known to be induced in skin by TNF derived from degranulating mast cells. Further attention should be directed toward the role of mast cell products, particularly TNF, in inflammation in the oral cavity.
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PMID:Relationship between mast cell degranulation and inflammation in the oral cavity. 756 63

In the 'sunburn' response in skin, dermal blood vessels are activated and traffic of dendritic Langerhans' cells altered. While these changes have been attributed to the cytokine TNF-alpha, the source of this acutely released TNF has not been identified. This report demonstrates that the 'sunburn' response, both in vivo and in vitro, is accompanied by rapid degranulation of cutaneous mast cells, with consequential release of intracellular stores of TNF. Epidermal keratinocytes were only minor contributors to local TNF production. Expression of the TNF-inducible CD62E (E-selectin/ELAM-1) and CD54 adhesion molecules on cutaneous endothelium occurred 2 h following mast cell degranulation, and this event was sensitive to blockade of mast cells with disodium cromoglycate. These results indicate that TNF release in skin in the acute sunburn response can largely be attributed to mast cells.
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PMID:Ultraviolet B irradiation of skin induces mast cell degranulation and release of tumour necrosis factor-alpha. 759 Aug 95

Clostridium difficile toxin A (Tx-A) mediates secretion and inflammation in experimental enterocolitis. Intravital video microscopy was used to define the mechanisms that underlie the inflammatory reactions elicited by direct exposure of the microvasculature to Tx-A. Leukocyte adherence and emigration, leukocyte-platelet aggregation, and extravasation of FITC-albumin were monitored in rat mesenteric venules exposed to Tx-A. Significant increases in leukocyte adherence and emigration (LAE) and albumin leakage were noted within 15-30 min of Tx-A exposure. These responses were accompanied by mast cell degranulation and the formation of platelet-leukocyte aggregates. The Tx-A-induced increases in LAE and albumin leakage were significantly attenuated by pretreatment with either monoclonal antibodies (mAbs) directed against the leukocyte adhesion glycoproteins, CD11/CD18, intercellular adhesion molecule-1, and P-selectin (but not E-selectin) or with sialyl Lewis x, a counter-receptor for P-selectin. The mast cell stabilizer, lodoxamide, an H1- (but not an H2-) receptor antagonist, and diamine oxidase (histaminase) were also effective in reducing the LAE and albumin leakage elicited by Tx-A. The platelet-leukocyte aggregation response was blunted by an mAb against P-selectin, sialyl Lewis x, and the H1-receptor antagonist. These observations indicate that Tx-A induces a leukocyte-dependent leakage of albumin from postcapillary venules. Mast cell-derived histamine appears to mediate at least part of the leukocyte-endothelial cell adhesion and platelet-leukocyte aggregation by engaging H1-receptors on endothelial cells and platelets to increase the expression of P-selectin. The adhesion glycoproteins CD11/CD18 and intercellular adhesion molecule-1 also contribute to the inflammatory responses elicited by toxin A.
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PMID:Clostridium difficile toxin A-induced microvascular dysfunction. Role of histamine. 796 37

Previous in vitro data indicate that degranulation of human mast cells triggers the induction of endothelial molecules important in leukocyte adhesion. In vivo experimental systems have not previously existed, however, to determine whether human mast cell degranulation is sufficient stimulus for leukocyte recruitment. To study this question, neonatal foreskins were transplanted onto immunodeficient mice. The grafts contained physiological numbers of human dermal mast cells that could be degranulated by a number of secretagogues that activate mast cells by different mechanisms. Degranulation was associated with an inflammatory response characterized by edema, up-regulation primarily of microvessel E-selectin, and influx of neutrophils. Leukocyte emigration associated with mast cell degranulation was inhibited by a monoclonal antibody against human E-selectin. These data indicate that degranulation of human mast cells in the human/SCID mouse model provokes cellular inflammation in skin. The ability to significantly inhibit early leukocyte infiltration with an antibody against E-selectin in this model supports the hypothesis that this molecule plays an important role in mast-cell-induced inflammation.
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PMID:Induction of E-selectin-dependent leukocyte recruitment by mast cell degranulation in human skin grafts transplanted on SCID mice. 854 5

Increased numbers of mast cells are noted at sites of wound healing and inflammation. These mast cells are either recruited from the bone marrow or proliferate locally under cytokine stimulation. However, the molecular mechanisms mediating initial adhesive interactions between mast cell precursors and vascular endothelial cells are not well understood. We have used a syngeneic dorsal skinfold chamber model of microcirculation to study early events of mast cell-endothelial cell interactions by intravital fluorescence microscopy. Because "rolling" represents the earliest step of granulocyte adhesion under conditions of flow, our objective was to determine whether vascular selectins promote rolling of immature mouse bone marrow-derived mast cells (MBMMC) on endothelial cells lining murine blood vessels in vivo. In this study, titanium window chambers were implanted on the dorsal skinfolds of BALB/c mice. The passage of injected fluorescently labeled MBMMC within blood vessels of the striated skin muscle was observed by stroboscopic epi-illumination. As previously determined for other leukocytes, MBMMC were observed to roll in venules but not in arterioles or capillaries. Mice were also treated with neutralizing anti-E-selectin (mAb 9A9) and anti-P-selectin (mAb 5H1) antibodies and tested for their ability to block MBMMC rolling on venular endothelial cells. Intravenous administration of mAb 5H1 resulted in a marked decrease in MBMMC rolling, whereas mAb 9A9 and isotype matched control antibodies had no effect on the rolling flux of MBMMC. These studies represent the first identification of P-selectin as a rolling receptor for MBMMC, and demonstrate the use of a dorsal skinfold technique to study MBMMC-endothelial cell interactions under conditions of physiologic flow. Further studies will determine whether vascular selectins participate in the rolling and tissue recruitment of true circulating immature mast cell precursors in vivo.
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PMID:Mouse bone marrow-derived mast cells roll on P-selectin under conditions of flow in vivo. 860 Mar 14

Eosinophils, neutrophils, and mast cells have all been implicated in the pathogenesis of bullous pemphigoid (BP). To comparatively characterize the involvement of these cells in BP, 10 lesional skin biopsy specimens were identified retrospectively and studied for tissue localization of eosinophil, neutrophil, and mast cell granule proteins. Subsequently, multiple skin biopsies of lesions in various developmental stages were obtained from 3 patients with untreated BP. Involved and uninvolved skin specimens were also obtained from 2 patients. Using indirect immunofluorescence, retrospectively identified lesions showed eosinophils and extracellular granule protein deposition prominently in areas of blistering. Evolving lesions showed eosinophil granule protein deposition in all stages but was most marked in early erythematous and prebullous (urticarial) lesions and was minimal in uninvolved skin. Vascular cell adhesion molecule-1, E-selectin, and P-selectin were detected on vessels and very late activation antigen-4 was detected on mononuclear cells and eosinophils by immunoperoxidase staining of lesions. Eosinophil granule proteins were increased in the peripheral blood, urine, and blister fluid. Blister fluids caused increased eosinophil survival that was inhibited by antibodies to interleukin-5 and interleukin-3. Although neutrophil and mast cell infiltration was observed, extracellular granule protein deposition from these cells was minimal except in two specimens. These results demonstrate that eosinophils infiltrate and deposit granule proteins early in the development of BP lesions, that eosinophil-activating cytokines are present in blister fluid, and that eosinophil-selective adhesion molecules are present. These studies strongly support a role for eosinophils in blister formation in BP.
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PMID:Deposition of eosinophil granule proteins precedes blister formation in bullous pemphigoid. Comparison with neutrophil and mast cell granule proteins. 877 44

Chronic proliferative dermatitis is a spontaneous mutation in C57BL/Ka mice (cpdm/cpdm), showing alopecia, epithelial hyperproliferation, infiltration by eosinophils and macrophages, and vascular dilatation. To further elucidate its pathogenesis, organs of 1-, 2-, 3-, 4-, 5-, and 6-week-old cpdm/cpdm mice were examined. At 4 weeks, the epidermal thickness was increased, whereas already at 3 weeks, the bromodeoxyuridine incorporation was increased in the basal keratinocytes. However, already at the age of 1 week, skin, lungs, and lymph nodes were infiltrated by eosinophils although no macroscopic lesions were present. Compared with control animals, 6-week-old cpdm/cpdm mice had decreased serum IgE levels and increased numbers of mast cells. From the age of 1 week these mast cells became increasingly IgE positive. In contrast, the mast cells of the control animals remained IgE negative. Mast cells of control and cpdm/cpdm mice were interleukin-4 and tumor necrosis factor-alpha positive. A likely explanation for the tissue infiltration of eosinophils could be the release of interleukin-4 and tumor necrosis factor-alpha from activated mast cells. Tumor necrosis factor-alpha may lead to the expression of E-selectin on endothelial cells, facilitating interleukin-4-mediated eosinophil transendothelial migration. Although various pathogenetic aspects of the cpdm/cpdm mouse need further elucidation, this model can be a tool to study eosinophil infiltration, leukocyte-endothelial cell interactions, and mast cell proliferation. Furthermore, the cpdm/cpdm mouse can be used to study chronic inflammatory skin disease because of the severe epidermal proliferation.
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PMID:Pathogenesis of skin lesions in mice with chronic proliferative dermatitis (cpdm/cpdm). 877 48

It has been shown recently that mast cells play an essential role as a source of tumor necrosis factor-alpha production during neutrophil recruitment to sites of bacterial infection. Increased numbers of mast cells are indeed noted at sites of wound healing and inflammation. These cells are either recruited from the bone marrow or proliferate locally under cytokine stimulation. Little is known about how mast cell progenitors extravasate into tissue. Using antibody-like fusion proteins of mouse E-selectin and P-selectin, we have analyzed the ability of immature mouse bone marrow-derived mast cells (BMMC) to interact with the endothelial selectins. The P-selectin glycoprotein ligand-1 (PSGL-1) was affinity-isolated from detergent extracts of surface biotinylated BMMC with both selectin-IgG fusion proteins. However, only P-selectin-IgG, but not E-selectin-IgG showed significant interaction with intact BMMC as tested by flow cytometry and cell attachment assays with the immobilized fusion proteins under flow and non-flow conditions at physiological shear stress. Thus, in spite of carrying the necessary carbohydrate modifications which enable solubilized PSGL-1 to bind avidly to E-selectin, PSGL-1 on the surface of BMMC is presented in a way that prevents it from interacting efficiently with E-selectin. Affinity-purified rabbit antibodies against mouse PSGL-1 almost completely blocked the interaction of BMMC with P-selectin-IgG in flow cytometry as well as in cell adhesion assays under static and under flow conditions. Our data reveal that PSGL-1 is the major binding site for P-selectin on mouse BMMC progenitors, but does not support efficient interactions with E-selectin.
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PMID:P-selectin glycoprotein ligand-1 mediates rolling of mouse bone marrow-derived mast cells on P-selectin but not efficiently on E-selectin. 920 82

Allergic rhinitis involves an early phase, largely mediated through mast cells, and a late phase which involves cellular infiltration and mediator release. In the early phase, mast cells release mediators as a result of antigen cross-linking adjacent immunoglobulin E molecules bound to mast cell surfaces. This results in an accumulation of histamine which gives rise to the characteristic symptoms of rhinitis--sneezing, itching, rhinorrhoea and congestion. The late phase of the allergic response (hours after challenge) involves infiltration of the nasal epithelium by eosinophils, basophils, monocytes and T-lymphocytes, which release leukotrienes, kinins, histamine and a host of other mediators. The most important part of the late-phase response is probably mediated via the production of cytokines (IL-4, IL-5, IL-6, IL-8, GM-CSF and RANTES) by mast cells, TH2 lymphocytes or epithelial cells. The infiltration of tissues by cells normally present only in the blood is brought about by the production of adhesion molecules, such as VCAM-1 and E-selectin, which cause circulating eosinophils, basophils and T-lymphocytes to adhere to endothelial cells before moving through the endothelium into the tissue (diapedesis). Neuronal reflexes also play a role in the allergic response, both by mediating local responses to mediators and possibly playing a part in the activation of T-lymphocytes. The allergic response has also been shown to be less intense in a hot, humid environment, and more marked in a cold, dry environment, possibly due to changes in osmolality of the nasal surface fluid. Similar factors may play a role in the aetiology of non-allergic rhinitis.
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PMID:Pathophysiology of perennial allergic rhinitis. 921 57


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