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)

Rat serosal mast cell beta-adrenergic receptors were characterized both functionally by assessing changes in histamine release and cyclic 3',5' adenosine monophosphate (cAMP) levels and directly by radioligand binding studies using [3H]dihydroalprenolol ([3H]DHA), a beta-adrenergic antagonist. Mast cells were obtained by lavage of the pleural and peritoneal cavities of Sprague-Dawley rats and were purified on metrizamide gradients to greater than 95% purity. Resting mast cells stimulated with beta-adrenergic agonists demonstrate a marked rise in cAMP levels after a 15-sec incubation. However, the same concentrations of these agonists have no effect on IgE-mediated mast cell histamine release. [3H]DHA binding to intact mast cells is rapid, reversible, saturable, and stereoselective. The cells possess 40,000 +/- 14,000 beta-adrenergic receptors/cell and demonstrate a binding affinity of 1.58 +/- 0.56 nM for [3H]DHA. Competition studies reveal that 83.5% of the receptors are of the beta 2 subtype and 16.5% are beta 1. Neither sensitization with anti-DNP-BSA IgE nor subsequent challenge with specific antigen alters mast cell beta-adrenergic receptor characteristics. Rat mast cells possesses large numbers of high affinity beta-adrenergic receptors, primarily of the beta 2 subtype, coupled to adenylate cyclase, but the role of these receptors in mast cell secretory events is not yet established.
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PMID:Characterization of the rat mast cell beta-adrenergic receptor in resting and stimulated cells by radioligand binding. 612 1

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

Transforming growth factor beta 1 (TGF beta 1) is a regulator of cell proliferation and differentiation. Using a mouse peritoneal cell-derived mast cell culture system, we investigated the effects of TGF beta 1 on mast cell proliferation. TGF beta 1 inhibited IL-3- and IL-4-dependent connective tissue-type mast cell proliferation. The effect was concentration dependent: 50% inhibition was observed with 1.0 ng/ml TGF beta 1 and the maximal inhibitory effect (no proliferation), was observed with 10 ng/ml. Flow cytometric analysis suggested that the inhibitory effect of TGF beta 1 was due to blocking of both G1 and G2 phases. Both control and TGF beta 1-treated mast cells showed similar histamine release induced by the calcium ionophore, A23187. TGF beta 1 seems to be an important negative regulator of connective tissue-type mast cell proliferation with apparently no appreciable effect on mast cell function.
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PMID:Transforming growth factor beta 1 inhibits IL-3- and IL-4-dependent mouse connective tissue-type mast cell proliferation. 753 49

Monolayer cultures of human epithelial and endothelial cells were used to study the association of latent transforming growth factor-beta 1 (TGF-beta 1) to extracellular matrices and its release and activation during matrix degradation. Human umbilical vein endothelial cells and embryonic lung fibroblasts produced relatively high levels of TGF-beta 1, its propeptide (beta 1-latency-associated protein), and latent TGF-beta-binding protein and incorporated latent TGF-beta 1 into their matrices as shown by immunoblotting. Amnion epithelial cells produced lower levels of these proteins. Confluent cultures of epithelial cells were exposed to matrix-degrading proteases and glycosidases. Mast cell chymase, leukocyte elastase, and plasmin efficiently released matrix-bound latent TGF-beta 1 complexes, while chondroitinase ABC and heparitinases were ineffective. The ability of the proteases to activate recombinant latent TGF-beta 1 was tested using growth inhibition assays and a novel sodium deoxycholate-polyacrylamide gel electrophoresis followed by immunoblotting. Sodium deoxycholate solubilized M(r) 25,000 TGF-beta 1 but did not dissociate high M(r) latent TGF-beta 1 complexes, allowing separation of these forms by polyacrylamide gel electrophoresis. Mast cell chymase and leukocyte elastase did not activate latent TGF-beta 1, suggesting that its release from matrix and activation are controlled by different mechanisms. The release of TGF-beta from the matrix by leukocyte and mast cell enzymes may contribute to the accumulation of connective tissue in inflammation.
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PMID:Human mast cell chymase and leukocyte elastase release latent transforming growth factor-beta 1 from the extracellular matrix of cultured human epithelial and endothelial cells. 787 40

Mast cells, which are capable of releasing a multitude of preformed and newly generated biological mediators and cytokines, are involved in various inflammatory processes. We studied whether histamine, a mast cell degranulation product, influences the adhesive interactions of T cells with extracellular matrix (ECM) glycoproteins, an event that occurs at sites of inflammation and is mediated primarily by virtue of cell-surface receptors of the beta 1-integrin subfamily. A prerequisite of lymphocyte-ECM interactions is activation of the cells, which modulates the affinity of the otherwise inactive integrins. Isolated rat CD4+ T cells were preincubated with histamine and activated with phorbol myristate acetate (PMA), and their ability to adhere to immobilized ECM components (fibronectin and laminin) was determined. Preincubation with histamine resulted in a 40-50% decrease in the adhesion of the CD4+ cells to both fibronectin or laminin. The notion that inhibition of T cell adhesion to ECM proteins by histamine-induced increase of the cells' intracellular levels of cAMP, thus interfering with calcium influx-associated events that occur during T cell activation, is supported by the finding that T cell adhesion was also abrogated by pharmacological inducers of cAMP. When the T cells were preincubated with supernatants of immunologically activated mast cells and then activated with PMA, a 40-50% inhibition of their adhesion to fibronectin or laminin was also observed. The inhibitory moiety present in the mast cell degranulation supernatants was resistant to heat (80 degrees C). Histamine exerted its suppressive effect on adhesion of T cells via their H2 receptors, as pretreatment with H2 antagonists abrogated the inhibitory effect. Thus, both purified histamine and mast cell-secreted histamine appear to be capable of affecting T cell interactions with ECM.
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PMID:Inhibition of T cell adhesion to extracellular matrix glycoproteins by histamine: a role for mast cell degranulation products. 793 Sep 46

The expression of the alpha 6 beta 4 and alpha 6 beta 1 integrins on epidermal Langerhans cells (LC) before and after mast cell degranulation was studied in cultured human neonatal foreskin by immunohistochemistry. Twenty-four hours after addition of mast cell secretagogues, morphine sulfate, or substance P, solitary mid-epidermal cells showed staining for the integrin subunits alpha 6, beta 4, and beta 1. This expression was not observed in cultured control explants, and immunostained cells were confirmed to be non-epithelial, dendritic cells by immuno-electron microscopy. The identity of these cells as LC was further established by coincident staining for alpha 6 and CD1a using double immunofluorescence labeling. Addition of tumor necrosis factor-alpha (TNF alpha), the predominant cytokine in mast cell granules, also induced LC to express alpha 6 integrins. Furthermore, preincubation of skin organ cultures with anti-TNF alpha antibodies or the mast cell inhibitor cromolyn sodium abrogated the ability to induce alpha 6 integrins on LC consequent to experimental mast cell degranulation by substance P. These data implicate a role for mast cell-derived TNF alpha in the regulation of the integrins alpha 6 beta 4 and alpha 6 beta 1 on LC. These findings may have important implications relevant to mechanisms for spatial localization of LC within the cutaneous compartments during immune responses.
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PMID:Mast cell degranulation upregulates alpha 6 integrins on epidermal Langerhans cells. 834 16

Pulmonary biopsy specimens from ten cases of idiopathic pulmonary fibrosis (IPF) were examined using routine histological stains, including toluidine blue, and immunohistochemistry by means of specific antibodies against alpha-smooth muscle (alpha-SM) actin, desmin, keratin, TGF beta 1, and TNF alpha. The sections were compared with two cases of normal lung. As shown previously, normal alveolar interstitium did not contain alpha-SM actin positive myofibroblasts nor did the alveolar lining contain any significant number of TGF beta 1 or TNF alpha laden epithelial cells. In IPF, during the inflammatory stage, the alveolar myofibroblasts expressed alpha-SM actin and the regenerating type II alveolar epithelium staining strongly with TGF beta 1 and TNF alpha antibodies. The former cytokine was also detected in the interstitial matrix and fibroblastic cells as well as in the wall of vessels. At this stage, a manifest mast cell infiltration was noted. In very fibrotic and cystic alveolar tissue, i.e., at end stage fibrosis, the number of alpha-SM actin positive myofibroblasts as well as that of TNF alpha laden type II epithelial cells diminished, while TGF beta 1 positive cells persisted. Our findings demonstrate that during IPF alveolar type II epithelium constitutes, if not the site of synthesis, at least the main reservoir for TGF beta 1 and TNF alpha. These cytokines, besides their involvement in fibrogenesis, play probably an important role in the expression of alpha-SM actin by alveolar myofibroblasts. Our study suggests the possibility of an interaction between interstitial cells and alveolar epithelium, during IPF.
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PMID:Cytoskeletal protein modulation in pulmonary alveolar myofibroblasts during idiopathic pulmonary fibrosis. Possible role of transforming growth factor beta and tumor necrosis factor alpha. 852 Jul 91

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

Interactions of cells with their extracellular matrix (ECM) are central to tissue-specific migration, localization, and function of migratory cells. Since mast cells circulate as immature precursor cells and home to tissues in a characteristic distribution, with increases in various disease states, we used the immature human mast cell line HMC-1 as a model to investigate the poorly understood mast cell-ECM interactions in humans. Functional adhesion studies showed that HMC-1 cells spontaneously adhere to fibronectin and laminin (80% at 6 and 12 microgram/ml, respectively) and to collagen type I and III (50% at 20 microgram/ml), whereas binding to vitronectin and collagen type IV required cell activation by phorbol myristate acetate. HMC-1 cells did not adhere to hyaluronic acid. Moreover, both fibronectin and laminin supported pronounced cytoplasmatic spreading with formation of isolated lamellipodia, whereas these cells exhibited a round cell shape on collagen and vitronectin, as shown by scanning electron microscopy. On flow cytometric analysis, HMC-1 cells expressed several adhesion molecules including the integrins beta 1, alpha 2 through alpha 6, alpha v, and alpha v beta 5, as well as CD44. Adhesion to fibronectin and vitronectin was found to be divalent cation- and arginine-glycine-aspartic acid-dependent, and could be blocked by antibodies to beta 1 or alpha 5, and alpha v or alpha v beta 5, respectively. In contrast, binding to laminin and collagen could not be blocked by monoclonal antibodies to any of the cell surface adhesion receptors expressed. Our results show that immature mast cells are able to modify their adhesive behavior in response to various ECM proteins and activating stimuli, and that this phenomenon is partly integrin mediated. These findings may be important for our understanding of the mechanisms leading to tissue-specific localization of mast cells.
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PMID:Interactions of immature human mast cells with extracellular matrix: expression of specific adhesion receptors and their role in cell binding to matrix proteins. 864 90

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


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