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)

An association between the release of histamine and chondroitin sulfate E proteoglycan (PG) was demonstrated in human colonic mucosa (HCM). Colonic biopsy samples incorporated [35S]sulfate (2.7 X 10(6) +/- 188 X 10(3) cpm/mg of wet tissue; mean +/- SEM, n = 5) into PG, which was partially released into the culture medium during the incubation period. Ascending thin-layer chromatography of the released 35S-labeled PG after its digestion by chondroitin ABC lyase (chondroitinase, EC 4.2.2.4) followed by autoradiography yielded three products that migrated in the position of monosulfated disaccharides of N-acetylgalactosamine 4-sulfate and N-acetylgalactosamine 6-sulfate and of an oversulfated disaccharide possessing N-acetylgalactosamine 4,6-disulfate. Cultured colonic mucosa released 23.6 +/- 3.7 ng of histamine per mg of wet tissue (mean +/- SEM, n = 16) without any specific trigger. Comparison by linear regression analysis of the release of histamine and chondroitin [35S]sulfate E PG revealed a correlation coefficient (r) of 0.7 (n = 16; P less than 0.005). Histological examination of the colonic biopsies revealed the presence of many mast cells in various degrees of degranulation in the mucosa and submucosa, most of which were found in the submucosa. Incubation of the HCM biopsies in the presence of anti-human IgE revealed 58% +/- 12% (mean +/- SEM, n = 3) enhancement in the release of chondroitin [35S]sulfate E PG and 64% +/- 10% (mean +/- SEM, n = 4) of histamine release. The above correlation, the observation that most of the mast cells showed various degrees of degranulation, and the lack of heparin synthesis as opposed to the synthesis and immunological release of chondroitin sulfate E strongly suggest that the E mast cell exists in the human colon.
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PMID:Histamine and chondroitin sulfate E proteoglycan released by cultured human colonic mucosa: indication for possible presence of E mast cells. 241 44

Metachromatically granulated cells were generated from human fetal liver stem cells cultured in heterologous mouse conditioned medium rich in interleukin 3. After 2 to 3 wk of culture with biweekly changes of medium and selection of nonadherent cells, all cells present in five cultures had cytoplasmic granules, and 60 to 95% of the cells stained metachromatically with toluidine blue or with alcian blue but not with the safranin counterstain. Ultrastructurally, many granules contained fibrillar material or electron-dense cores with fibrils and vesicular fragments. In addition, the granules of many cells were filled with electron-dense material, which in some cases had a fine structure consisting of concentric whorls or a reticular pattern. Analysis of high-affinity IgE receptors on the cultured cells by flow cytometry demonstrated a unimodal fluorescence pattern, suggesting that most cells were in the basophil or mast cell lineage. The cultured cells lacked the lymphoid cell surface determinants B1, B4, T3, and T11, the myeloid determinants Mo2 and MY9, the natural killer cell determinant 901, and Ia histocompatibility antigens, but expressed the myeloid determinant MY7. The cells contained 52 ng/10(6) cells of histamine and incorporated [35S]sulfate at an average rate of 31,300 cpm/10(6) cells/4 hr into 175,000 m.w. chondroitin sulfate A proteoglycans. Upon activation with 1 microM calcium ionophore A23187, the cultured cells released 53% of their cell-associated histamine and metabolized arachidonic acid to 15.0 ng/10(6) cells of immunoreactive leukotriene C4 equivalents, 0.5 ng/10(6) cells of leukotriene B4, and 3.1 ng/10(6) cells of prostaglandin D2 (means, n = 3). Thus, stem cells present in human fetal liver give rise, as do stem cells in mouse fetal liver, to metachromatically granulated cells when cultured in the presence of mouse interleukin 3. In both species, the cultured cells bear IgE receptors, lack characteristic lymphoid and most myeloid cell surface determinants, and contain histamine and chondroitin sulfate proteoglycans. The human fetal liver-derived cells are similar in morphology and T cell factor dependence to basophil-like cells derived from umbilical cord blood, but are novel in their capacity to generate leukotrienes and prostaglandin D2.
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PMID:Biochemical and phenotypic characterization of human basophilic cells derived from dispersed fetal liver with murine T cell factors. 241 26

In inside-out red cell membrane vesicles active calcium transport and the formation of the enzyme-phosphate complex (EP) of the calcium pump were simultaneously investigated and the effects of a limited proteolytic digestion examined. In order to visualize the proteolyzed EP forms we have induced the formation of a maximum level EP from [gamma-32P]ATP in the presence of Ca2+ + La3+ and applied a good-resolution acidic discontinuous sodium dodecyl sulfate-polyacrylamide gel electrophoresis system. Proteolysis of inside-out vesicle membranes by trypsin, Pronase, papain, or chymotrypsin produces a calmodulin-like activation of the calcium pump, abolishes its calmodulin sensitivity, and decreases the original 140-kDa EP complex to a limit polypeptide of 80 kDa. Trypsin digestion produces another major intermediary fragment of 90 kDa, which is still a low-activity calmodulin-sensitive form of the pump. The red cell calcium pump is activated by trypsin both in the absence and presence of Ca2+ during digestion although the rate of activation and the appearance of the 80-kDa polypeptide are enhanced by Ca2+. If proteolytic digestion is carried out by chymotrypsin, a calmodulin-insensitive maximum activation of the calcium pump coincides with the formation of a 125-130-kDa EP-forming polypeptide. Chymotrypsin and carboxypeptidase A have synergistic effects on the formation of this latter high-activity species. Based on these data we suggest a probable molecular arrangement for the functional parts of the red cell membrane calcium pump.
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PMID:Molecular characterization of the in situ red cell membrane calcium pump by limited proteolysis. 242 14

Intravenous administration of morphine sulfate often produces urticarial and hypotensive reactions associated with elevations in plasma histamine. The source of this histamine and mechanisms controlling its release are poorly understood. Previous studies of morphine-induced histamine release compared human leukocytes to rat peritoneal mast cells. The effects of morphine on human cutaneous mast cells has not been examined. We studied in vitro histamine release from human basophils and human skin preparations containing cutaneous mast cells to evaluate their relative contribution to the pharmacologic effects of morphine. Human skin mast cell preparations showed dose-dependent histamine release over a morphine concentration range of 1.5 X 10(-5) to 4.5 X 10(-3) M, with peak release occurring at 5 X 10(-4) M, with peak release occurring at 5 X 10(-4) M. Clinically, morphine sulfate is usually injected as a 1.5 X 10(-2) M solution. Histamine release was calcium dependent and equivalent to that obtained with 3 and 10 mM strontium. Morphologic examination revealed degranulation and exocytosis occurring in morphine-stimulated tissue but not in specimens exposed to buffer alone. Lactate dehydrogenase levels did not increase following morphine incubation, thus supporting a noncytolytic mechanism of histamine release. Basophils, in contrast, showed no significant histamine release from exposure to morphine up to 10(-2) M. Concanavalin A, as a positive control in these same preparations, produced a mean histamine release of 21.0%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Functional differences between human cutaneous mast cells and basophils: a comparison of morphine-induced histamine release. 242 25

The responses of human cutaneous, pulmonary, intestinal, and cardiac tissue mast cells to the histamine-releasing agent morphine sulfate (MS) were investigated in vitro. Human cutaneous mast cells released significant amounts of histamine in the presence of 1 to 100 mumol/L concentrations of MS. Histamine release was detectable within 5 minutes after challenge and was complete by 15 minutes. A maximal histamine release of 21.6% (+/- 1.4 SEM) was observed after stimulation with 100 mumol/L of MS. This MS effect was inhibited by the opiate receptor antagonist naloxone with a 59% inhibition detected at equimolar concentrations and an 88% inhibition occurring in the presence of a tenfold molar excess of naloxone. Naloxone did not alter the cutaneous mast cell response to the calcium ionophore A23187. Human mast cells derived from pulmonary, intestinal, and cardiac tissues, as well as blood basophils, did not release histamine after stimulation with 1 to 200 mumol/L of MS, whereas each of these cell preparations responded to an IgE-mediated stimulus. The results of this study demonstrate that cutaneous mast cells release inflammatory mediators after stimulation by MS, whereas mast cells residing in lung, heart, and gastrointestinal tissues do not. These observations indicate that human mast cells in different anatomic sites can vary in their functional responses.
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PMID:Functional heterogeneity of human mast cells from different anatomic sites: in vitro responses to morphine sulfate. 243 77

Keratinocytes are capable of releasing distinct immunomodulating cytokines such as epidermal cell-derived thymocyte activating factor (ETAF) and an epidermal cell-derived natural killer cell augmenting factor (ENKAF). The present study was performed to determine whether human keratinocytes also may secrete an interleukin 3 (IL-3)-like mediator and thereby participate in the regulation of mast cell activity in the skin. Supernatants of freshly isolated human epidermal cells (EC) and malignant keratinocyte cell lines (A 431, SCC) were tested for their capacity to induce the proliferation of IL-3-dependent cell lines 32 DCL and FDCP. Human epidermal cell interleukin 3 (EC IL-3) is spontaneously released by freshly isolated EC, A 431, and squamous cell carcinoma (SCC) cells. However, both normal EC and A 431 cells produced increased levels of EC IL-3 activity when cultured in the presence of different stimulants, such as phorbol myristate acetate and lipopolysaccharide. The EC IL-3 activity was not inhibited when treated with a monoclonal anti-IL-1 or anti-IL-2-antibody. Biochemical characterization showed that human EC IL-3 has a molecular weight of 17K, elutes of DEAE-ion exchange high-performance liquid chromatography (HPLC) as one major peak at 0.36 M NaCl, and upon HPLC-chromatofocusing exhibits 3 isoelectric points of 7.8, 7.5, and 5.6. Upon reversed-phase HPLC, EC IL-3 activity eluted at about 100% acetonitrile. When highly purified EC IL-3 was labeled with 125I and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, a single homogeneous band exhibiting a molecular weight of 17K was seen, which correlated with the IL-3 activity and was free of ETAF/IL-1, IL-2, and interferon activity. These data indicate that human EC synthesize an IL-3-like cytokine which is distinct from ETAF/IL-1, IL-2, and interferon and thereby may participate in the regulation of mast cell activity during inflammatory and fibrotic, as well as hypersensitivity reactions.
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PMID:Human keratinocytes and epidermoid carcinoma cell lines produce a cytokine with interleukin 3-like activity. 243 14

Mature connective tissue mast cells (CTMC) have not been previously available as a cell line from any species. Here we describe 15 novel mast cell lines (KiSV-MC) that were derived by coculturing murine splenocytes with fibroblasts that produce a Ki-ras-containing murine sarcoma virus. Some of the KiSV-MC lines are similar to CTMC in that they synthesize predominantly heparin proteoglycans, and contain up to 35 micrograms of histamine and 2.2 units of carboxypeptidase A/10(6) cells in secretory granules which stain red with Safranin. Other cell lines display phenotypic characteristics intermediate to CTMC and mucosal-like mast cells in being predominantly Safranin-, having lower amounts of histamine and carboxypeptidase A, and in synthesizing chondroitin sulfate E proteoglycans in preference to heparin proteoglycans. When the individual KiSV-MC lines were compared, a linear relationship was found between the number of Safranin+ granules, the cellular contents of histamine and carboxypeptidase A, and the biosynthesis of heparin relative to chondroitin sulfate E proteoglycans. Upon sensitization with monoclonal IgE and exposure to hapten-specific antigen, the cells exocytose the contents of their secretory granules. Thus, these immortalized cells provide the first source of CTMC-like lines for chemical and functional analysis and illustrate that murine mast cells can express a continuum of phenotypes.
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PMID:Immortalization of murine connective tissue-type mast cells at multiple stages of their differentiation by coculture of splenocytes with fibroblasts that produce Kirsten sarcoma virus. 245 91

A simple, minimally invasive procedure for monitoring cutaneous mast cell degranulation in vivo in man is described. Plasma histamine levels in venous blood draining the site of intradermal histamine, morphine, and antigen challenges were determined with a modified radioenzymatic assay. Elevations in plasma histamine above baseline levels of 0 to 0.6 ng/ml were measured after intradermal histamine; levels of 1.4 to 85.2 ng/ml were obtained after a 2 microgram intradermal challenge in 16 subjects. After antigen testing, peak plasma histamine levels ranged from 1.1 to 24.4 ng/ml (n = 9), and after morphine sulfate skin testing peak plasma histamine levels ranged from 2.3 to 12.7 ng/ml (n = 4). The time to achieve peak plasma histamine levels ranged from 2 to 10 minutes after histamine, from 5 to 15 minutes after antigen, and from 1 to 8 minutes after morphine challenges. Plasma levels returned to baseline within 30 minutes after histamine and morphine challenges but took more than 60 minutes for antigen challenges. With careful choice of the skin test site in relation to venous drainage, plasma histamine increases after either histamine or antigen were reproducible and reliable. Plasma histamine levels peaked 5 to 10 minutes before maximal development of the wheal-and-flare responses after histamine, antigen, or morphine skin tests. The wheal-and-flare skin tests continued to increase in magnitude despite rapidly declining plasma histamine levels. Thus skin tests eliciting reactions ordinarily seen in an allergist's office cause measurable increases in plasma histamine levels that can be used to directly monitor mast cell degranulation in man in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Use of plasma histamine levels to monitor cutaneous mast cell degranulation. 246 33

The Basenji greyhound (BG) has been proposed as a model of atopic disease because of its chronic relapsing atopic dermatitis as well as airway hyperresponsiveness. We attempted to characterize this model further by comparing its skin wheal-and-flare responses to morphine sulfate and histamine with those of control, nonatopic mongrel dogs. We found that BG dogs had significantly smaller skin responses than did the control dogs to all but two concentrations of histamine used. In contrast, BG dogs demonstrated greater skin response to morphine at the three lowest concentrations used but had a significantly smaller skin response at the highest dose of morphine. Skin punch biopsy specimens revealed decreases in histamine content after morphine exposure but no difference in histamine content of the unexposed skin or of morphine-exposed skin for the two groups of dogs. When percent histamine release was compared, however, BG dogs were found to release a significantly greater proportion of histamine in response to morphine than control dogs. Although there was no significant difference in total mast cell counts for the two groups, the BG dogs had significantly fewer formalin-insensitive mast cells in unexposed skin than control dogs. We conclude that skin responses in BG dogs are characterized by decreased end organ responsiveness and greater releasability of mast cells in response to nonimmunologic stimulation.
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PMID:Dermal mast cell releasability and end organ responsiveness in atopic and nonatopic dogs. 246 81

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


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