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)

We have evaluated the adhesion of human cutaneous mast cells to several components of the extracellular matrix (plasma fibronectin, laminin, collagen type I and IV) and studied whether these cells express the beta 1 integrins potentially involved in the adhesion to these proteins. Human skin mast cells (5.1 +/- 1.5% pure) spontaneously adhered to fibronectin and laminin (0.1 to 10 micrograms/ml) immobilized on plastic surfaces (e.g., 14 +/- 7.2% and 14 +/- 4.4% adhesion at 10 micrograms/ml, respectively). Similar results were obtained with a 90% pure mast cell preparation. In contrast, cutaneous mast cells did not adhere to collagen type I (1.6 +/- 0.5% adhesion) or type IV (1.2 +/- 0.8% adhesion). Control adhesion in BSA-coated wells was < 5%. Mast cell adhesion to fibronectin was optimal after an incubation period of 60 to 90 min (t1/2 = 28.2 +/- 6.2 min), whereas adhesion to laminin was faster (t1/2 = 10.1 +/- 1.2 min), being nearly optimal after a 15-min incubation period. Human skin mast cell adhesion to fibronectin and laminin was found to be dependent on the presence of divalent cations in the extracellular medium. Dual-color immunofluorescence and flow cytometry were used to evaluate whether human skin mast cells (51.3 +/- 3.9% pure) express beta 1 integrins that may mediate cell adhesion to extracellular matrix proteins. These mast cells were found to express VLA (very late Ag)-3 (75.3 +/- 35.6 specific fluorescence intensity) and, to lesser degree, VLA-4 and VLA-5 receptors (8.0 +/- 2.5 and 6.9 +/- 3.2 specific fluorescence intensity, respectively). In contrast, VLA-1, VLA-2, and VLA-6 integrins were not expressed significantly. mAb to VLA-3, VLA-4, and VLA-5 each inhibited by 70% skin mast cell adhesion to fibronectin. mAb to VLA-3 nearly abolished mast cells adhesion to laminin, whereas anti-VLA-4 and anti-VLA-5 were ineffective. Finally, immunosuppressant cyclosporin A (100 nM) and FK-506 (10 nM) significantly inhibited mast cell adhesion to both fibronectin and laminin (p < 0.05). Our data demonstrate that human skin mast cells spontaneously adhere to fibronectin and laminin, and that this adhesion is mediated by VLA-3, VLA-4, and/or VLA-5 integrins on these cells. Interactions between these beta 1 integrins and extracellular matrix proteins may be involved in perivascular tissue localization of human mast cells in vivo.
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PMID:Human skin mast cells express functional beta 1 integrins that mediate adhesion to extracellular matrix proteins. 753 41

In this immunohistochemical light microscopic study we applied a panel of monoclonal antibodies to study the expression pattern of adhesion molecules in normal human conjunctiva from 15 patients. The molecules we analyzed included the VLA-family VLA-1-6, the leukocyte integrins LFA-1, Mac-1 and p150,95, the immunoglobulins LFA-3, CD2, ICAM-1 and VCAM-1 and the selectin ELAM-1. Our results show that only VLA-2, VLA-3, LFA-3, and the VLA-alpha 6 subunit are expressed on the epithelium. A strongly basal accentuation of the VLA-alpha 6 subunit indicates its possible relevance in anchoring the epithelium at the substantia propria. Intraepithelial T cells were VLA-1, VLA-5, LFA-1, and CD2 positive. Endothelial cells expressed VLA-1, VLA-2, VLA-3, VLA-5, VLA-alpha 6, ICAM-1, and LFA-3. ELAM-1 was seen only in specimens from five patients. Interestingly, mast cells were positive for VLA-3 and VLA-5, both of which are receptors for fibronectin, indicating that these integrins play an important role in mast cell function. Our study builds the basis for further investigations in adhesion molecules in conjunctival diseases.
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PMID:Adhesion molecules in normal human conjunctiva. An immunohistological study using monoclonal antibodies. 833 47

We report here the isolation of two new monoclonal antibodies (MB1.1 and MB1.2) against mouse VLA-beta 1 integrin subunit. Characterization by flow cytometry demonstrated binding of MB1.1 and MB1.2 to freshly isolated thymocytes, primary bone marrow mast cell lines, as well as cell lines of distinct lineage each expressing different combination of VLA integrins. The specificity of MB1.1 and MB1.2 was determined by (1) their binding to antigen with M(r) about 120 kDa, and (2) the ability of antiserum against the carboxyl terminal of VLA-beta 1 subunit to deplete antigens for MB1.1 and MB1.2 in sequential immunoprecipitation experiments. The epitopes for MB1.1 and MB1.2 were in close proximity to each other since preincubation of cells with one MAb inhibited the binding of the other. However, MB1.1 and MB1.2 differed in their affinity for the beta 1 subunit. In addition, neither MAbs had any effect on cell adhesion to matrix proteins indicating that the epitopes involved are distant from VLA integrin ligand-binding sites. MB1.1 and MB1.2 appear to differ from the two MAbs so far reported against mouse VLA-beta 1 subunit, KMI6 and 9EG7. Thus, the epitopes for MB1.1 and MB1.2 were readily detectable on unfractionated thymocytes whereas KMI6 has been reported to bind only a fraction of CD4-8- and CD4-8+ thymocytes. Phorbol ester and Mn2+, which have been shown to regulate the binding of 9EG7, had no effect on MB1.1 and MB1.2 binding to VLA-beta 1 integrin subunit.
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PMID:VLA-beta 1 integrin subunit-specific monoclonal antibodies MB1.1 and MB1.2: binding to epitopes not dependent on thymocyte development or regulated by phorbol ester and divalent cations. 874 92

Cytokines have been shown to have major roles in the development of mast cells from bone marrow progenitors. Immature mast cells derived from bone marrow thus leave the blood system to complete their course of maturation within tissues. However, it is now clear that VLA (beta 1) integrins with function in mediating cell-cell and cell-extracellular matrix protein interactions have effects on the growth and differentiation of diverse cell types. At present, the involvement of VLA integrins during mast cell development is still unclear. In this study, we report the preparation of a new monoclonal antibody (mAb) against mouse VLA-5 (alpha 5 beta 1) integrin. Together with mAb R1-2, we characterized the expression of VLA-4 (alpha 4 beta 1) and VLA-5 integrins, the two major fibronectin receptors, on two long-term cultured mast cell lines, CFTL-15 and MC/9. CFTL-15 cells were found to express both VLA-4 and -5 integrins whereas MC/9 cells expressed only VLA-5 but not VLA-4. We speculated that VLA integrin expression may be related to mast cell development. Thus bone marrow-derived mast cells (BMMC) were characterized after varying periods of development induced by IL-3. During the first 3 weeks the expression of VLA-4 and VLA-5 increased progressively and both were involved in mediating adhesion of BMMC to fibronectin. At time periods of greater than 3 weeks, the expression of VLA-4 declined gradually to little, if any, by week 13. In comparison, VLA-5 remained stably expressed and functioned as the major receptor for fibronectin. Results from this study therefore suggest that BMMC differentially utilize VLA-4 and VLA-5 integrins during IL-3-induced development. Differential expression of VLA integrins may have effects on the recirculation properties, tissue distribution and eventual maturation of progenitors to fully matured mast cells.
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PMID:Differential utilization of VLA-4 (alpha 4 beta 1) and -5 (alpha 5 beta 1) integrins during the development of mouse bone marrow-derived mast cells. 885 75

The development of mast cells from bone marrow precursors and their function as the mucosal- or connective-tissue-type mast cell are critically dependent on microenvironmental factors. Extracellular matrix proteins, such as collagen, fibronectin, and laminin, may represent insoluble components of the microenvironment. Recent studies have described multiple isoforms of laminin isolated from different tissues. In the present study, adhesion of mouse bone marrow-derived mast cells (BMMC) and long-term mast cell lines to Engelbreth-Holm-Swarm (EHS) tumor laminin, rat laminin, human merosin, and human placental laminin was compared. The greatest level of adhesion was found with human laminin as the substrate. By use of a newly prepared mouse VLA-alpha 6 integrin-specific mAb (MA6) together with the previously described mAb GoH3, VLA-6 (alpha 6 beta 1) integrin was found to be expressed and utilized by BMMC and long-term mast cell lines. VLA-6 has been described as a major laminin receptor with roles in diverse cell functions including cell growth and differentiation. BMMC have been shown to express a 32/67-kDa laminin receptor. Therefore, in addition to the 32/67-kDa laminin receptor described in early studies, BMMC also express VLA-6 integrin, which may have roles in the regulation of their development.
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PMID:Integrin VLA-6 (alpha 6 beta 1) mediates adhesion of mouse bone marrow-derived mast cells to laminin. 889 18

Mast cells (MC) and blood basophils (Ba) are multifunctional effector cells of the immune system and accumulate in areas of ongoing disease. However, despite of similar morphology, MC and Ba differ from each other in terms of cell surface receptor expression, mediator content, and tissue distribution. In order to gain new insights into mechanisms and molecules responsible for the distribution and accumulation of MC and Ba, we have investigated expression of homing receptors on primary human MC (lung, n=28; uterus, n=17), Ba (healthy donors, n=64), the mast cell line HMC-1, and the basophil line KU-812. Expression of cell surface antigens on MC and Ba was analyzed by mAb and indirect immunofluorescence staining techniques. In addition to previous findings, Ba were found to react with mAb against the selectin-ligands sLe(x) (CD15s) and PSGL-1 (CD162), L-selectin (CD62L), beta7-integrin, the 'matrix-receptor' neurothelin (CD147), platelet-endothelial cell tetraspan antigen-3 (PETA-3=CD151), and BST-1 (CD157). Novel antigens detectable on MC (lung and uterus) were CD147, CD151, CD157 and CD49c (VLA-3alpha). By contrast, MC were not recognized by mAb to sLe(x), PSGL-1, L-selectin, or beta7 integrin. No reactivity of Ba or MC with mAb to syndecan-1 (CD138), VE-cadherin (CD144), MUC18/MCAM (CD146), MGC-24 (CD164), or ALCAM (CD166) was found. The cell lines HMC-1 and KU-812 expressed a similar profile of antigens when compared to primary cells. In summary, Ba and MC express a unique profile of homing molecules. Apparently, Ba differ from MC in expression of recognition receptors relevant for binding to endothelium and consecutive transmigration.
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PMID:Expression of homing receptors and related molecules on human mast cells and basophils: a comparative analysis using multi-color flow cytometry and toluidine blue/immunofluorescence staining techniques. 1059 89