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)

Human mast cells have been purified from uterine tissues, and their surface marker profile and function have been evaluated as part of ongoing studies of mast cell heterogeneity. Using a panel of antibodies, purified uterine mast cells (UMC; 81% +/- 7% purity, n = 10) were analyzed by immunofluorescence and flow cytometry for surface expression of various antigens. Consistent with previous analyses of mast cells from other tissues, UMC expressed HLA class I, IgE, c-kit receptor, CD9, CD33, CD43, CD45, and CD54, while CD11a, CD11b, CD14, CD16, CD23, and CD64 were not detected. Unlike other mast cells, UMC expressed CD11c/CD18 (p150,95) and CD32 (Fc gamma RII). Additional antigens not previously studied on mast cells included the selectin LECAM-1 (Leu-8) and several beta 1 and beta 3 integrins; expression of very late activation antigen-4 (VLA-4) (CD49d/CD29), VLA-5 (CD49e/CD29), and the vitronectin receptor (CD51/CD61) was seen. Functional studies showed that treatment of human umbilical vein endothelial cells with interleukin-1 (5 ng/mL for 4 hours) resulted in a twofold to threefold increase in adhesiveness for UMC. Purification procedures did not alter histamine release responses to anti-IgE or the calcium ionophore A23187, and treatment of UMC with an anti-CD32 monoclonal antibody (IV.3) did not induce histamine release or alter anti-IgE-induced release. These data suggest that UMC may possess unique phenotypic characteristics, and support the concept of mast cell heterogeneity.
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PMID:Immunophenotyping and functional analysis of purified human uterine mast cells. 137 Jun 42

The screening of a rat mast cell cDNA library with a probe selected to recognize those genes preferentially or exclusively expressed by mast cells identified a rat gene sequence, RF-17, that shared homology with the beta-integrins. This integrin was expressed in rat tissues enriched for mast cells and T cells. The rat RF-17 sequence was used to isolate the murine homologue from a spleen cDNA library. The murine gene encodes a protein of 806 amino acids that is the probable homologue to the human beta 7 chain. Transcripts specific for the murine gene are found in the thymus, spleen, and lung. To attempt to identify the gene product for this new integrin chain, we examined the murine T cell line TK-1, which expresses a novel integrin heterodimer, lymphocyte Peyer's patch high endothelial venule adhesion molecule (LPAM-1), of a known alpha 4 chain and an unknown beta P chain, for expression of murine beta 7 (RF-17). This cell line expresses high levels of RF-17 transcripts, suggesting that beta P is encoded by the beta 7 gene. Bone marrow cells induced to differentiate into mast cells via IL-3 express the beta 7 gene as well as the genes encoding the murine integrin alpha 4 and beta 1 proteins. Surface staining analysis indicates that these cells express an alpha 4-containing integrin complex throughout the differentiation process. These data suggest that the Peyer's patch homing LPAM-1 receptor expressed by a subset of T cells consists of the beta 7 gene product and the alpha 4 chain, and that this integrin chain complex is also found on the surface of maturing mast cells. The presence of beta 1 transcripts also suggests that these maturing mast cells possess the LPAM-2 integrin complex (alpha 4/beta 1) as well. The experimental strategy described in this manuscript has, thus, identified a novel murine beta-integrin chain that is expressed by rodent T cells and mast cells.
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PMID:Expression of murine beta 7, alpha 4, and beta 1 integrin genes by rodent mast cells. 138 90

Kit, the receptor for stem cell factor (SCF) and the product of the c-kit proto-oncogene, is expressed on fetal liver-derived mast cell progenitors when cultured with SCF. Decreased levels of Kit on the surface of human fetal liver-derived mast cells after exposure to recombinant human SCF were demonstrated by flow cytometry using the YB5.B8 mAb against Kit. Internalization of Kit along with SCF appears to be the principal means by which Kit is lost from the mast cell surface. Neither the beta 3-integrin CD51/CD61 (alpha v beta 3), nor the beta 1-integrins CD49d,e/CD29 (VLA-4 and -5) appeared to be internalized along with Kit-SCF complexes. Reappearance of Kit on day 28 fetal liver-derived mast cells is complete 3 days after exposure of the cells to SCF and is detectable by 2 days. Recovery requires new protein and new RNA synthesis, because Kit did not reappear if cycloheximide or actinomycin D was added to the cells. No substantial change in total Kit mRNA was detected during the resynthesis period, suggesting that post-transcriptional regulation of Kit production is involved. Internalization of Kit in mast cells exposed to soluble SCF may represent a negative regulatory mechanism for this receptor-ligand interaction and down-regulate mast cell properties such as degranulation to SCF.
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PMID:Internalization of Kit together with stem cell factor on human fetal liver-derived mast cells: new protein and RNA synthesis are required for reappearance of Kit. 861 71

The integrin adhesion molecules are involved in the recruitment and activation of inflammatory cells at sites of inflammation in a variety of diseases. In the present study, we have investigated the effects of blocking monoclonal antibodies (mAbs) directed against CD49d (alpha(4) integrin), CD18 (beta(2) integrin) and the alpha sub-units of beta(2) integrin CD11a (LFA-1 integrin) and CD11b (Mac-1 integrin), on antigen (Ag)-induced acute bronchoconstriction and cellular recruitment in allergic rabbits in vivo. Inhaled Ag (Alternaria tenuis) challenge of neonatally sensitised rabbits caused an acute bronchoconstriction demonstrated by an increase in lung resistance (R(L)) and decrease in dynamic compliance (C(dyn)) and pulmonary inflammation characterised by an increase in bronchoalveolar lavage (BAL) inflammatory cells, particularly eosinophils, 24 h after challenge. Pre-treatment with the anti-CD49d mAb (Max-68P), significantly inhibited the Ag-induced acute bronchoconstriction in terms of R(L) and (C(dyn)). Treatment with the other anti-integrin mAbs had no effect on the acute bronchoconstriction after inhaled Ag challenge.Pre-treatment with the anti-integrin mAbs had differential effects in blocking the recruitment of inflammatory cells 24 h after inhaled Ag in the allergic rabbits. The data show that in the allergic rabbit model of asthma, VLA-4 (CD49d/CD29) only, is involved in the acute bronchoconstriction, suggesting an involvement of mast cell degranulation. Furthermore, eosinophil recruitment and activation appears to be mediated by a combination of VLA-4 (CD49d/CD29) and LFA-1 (CD18/CD11a). However in contrast, lymphocyte recruitment appears to be mediated by a combination of LFA-1 (CD18/CD11a) and Mac-1 (CD18/CD11b).
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PMID:The effect of anti-integrin monoclonal antibodies on antigen-induced pulmonary inflammation in allergic rabbits. 1287 19

We have used the parasite helminth Trichinella spiralis to study the generation and differentiation of mast cell progenitors in the bone marrow of mice, as this infection triggers an intestinal mastocytosis which correlates with parasite expulsion. C-kit+ mast cell progenitors have previously been defined by methylcellulose colony-forming units and by limiting dilution assays in vitro. In vivo experiments have demonstrated the essential requirement by mast cells for specific integrin expression. We have defined 2 c-kit+ populations in the bone marrow, one of which coexpresses CD49d/beta7 integrin, a marker essential for small intestine immigration. We have confirmed the phenotype of these cells by using antagonistic anti-c-kit antibody in vivo. Our data show that the loss of c-kit+/beta7+ cells from the bone marrow correlates with their appearance in the blood and precedes detection of mature mast cells in the gut by 3 days. This exit correlates with an increase in soluble stem cell factor (SCF) in the serum, suggesting that the c-kit/SCF interaction may be chemotactic or haptotactic in nature. This study shows that during infection the bone marrow environment generates mast cells destined for the intestinal mucosa before their exit into the periphery, indicating a clear interplay between infection site and hematopoietic tissue.
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PMID:In vivo exit of c-kit+/CD49d(hi)/beta7+ mucosal mast cell precursors from the bone marrow following infection with the intestinal nematode Trichinella spiralis. 1460 54

Mast cells, which are associated with T helper cell type 2-dependent inflammation, have now been implicated in the innate immune response. To further characterize how mast cells are programmed to respond to infectious organisms, we used expression profiling using DNA microarray analysis of gene expression by human mast cells (huMC) during ingestion of Escherichia coli and examined immunoglobulin E (IgE)-mediated degranulation. Analysis of data revealed that specific groups of genes were modulated, including genes encoding transcription factors, cell signaling molecules, cell cycle regulators, enzymes, cytokines, novel chemokines of the CC family, adhesion molecules, and costimulatory molecules. Enzyme-linked immunosorbent assay analysis confirmed the production of tumor necrosis factor and the chemokines CC chemokine ligand (CCL)-1/I-309, CCL-19/macrophage-inflammatory protein-3beta (MIP-3beta), and CCL-18/MIP-4; flow cytometry confirmed the up-regulation of carcinoembryonic antigen-related cell adhesion molecule 1, the integrin CD49d, and CD80. Coincubation with E. coli down-regulated Fc receptor for IgE I (FcepsilonRI) expression and FcepsilonRI-mediated huMC degranulation. These data are consistent with the concept that bacterial exposure directs mast cell responses toward innate immunity and away from IgE-mediated effects.
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PMID:Mast cells, which interact with Escherichia coli, up-regulate genes associated with innate immunity and become less responsive to Fc(epsilon)RI-mediated activation. 1628 32

We investigated the functions of critical adhesion molecules ICAM-1 and VCAM-1 in a keratin-14 IL-4-transgenic (Tg) mouse model of atopic dermatitis, the skin lesions of which are characterized by prominent inflammatory cell infiltration, significantly increased mRNAs and proteins of ICAM-1, VCAM-1, E-selectin, P-selectin, L-selectin, and PSGL-1, and significantly increased numbers of dermal vessels expressing these adhesion molecules. We tested the hypotheses that deletion or blockade of these molecules may impede the inflammation by examining the disease progresses in the Tg mice crossed with ICAM-1-knockout mice and Tg mice received anti-VCAM-1-neutralizing antibody. Although the findings of the ICAM-1-knockout Tg mice (Tg/ICAM-1(-/-)) developed skin lesions similar to wide-type ICAM-1 Tg mice (Tg/ICAM-1(+/+)) were surprising, a compensatory mechanism may account for it: the frequency of VCAM-1 ligand, CD49d, on CD3(+) T cells in the lesional skin significantly increased in the Tg/ICAM-1(-/-) mouse, compared with the Tg/ICAM-1(+/+) mice. In contrast, anti-VCAM-1-treated Tg/ICAM-1(-/-) or Tg/ICAM-1(+/+) mice had significantly delayed onset of skin inflammation compared with isotype antibody-treated groups. Moreover, anti-VCAM-1 significantly reduced the skin inflammation severity in Tg/ICAM-1(+/+) mice, accompanied with reduction of mast cell, eosinophil, and CD3(+) T cell infiltration. VCAM-1 is more critical in developing skin inflammation in this model.
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PMID:VCAM-1 blockade delays disease onset, reduces disease severity and inflammatory cells in an atopic dermatitis model. 2006 94