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)

A comparison was made between collagenase-dispersed guinea-pig atrial and ventricular tissues. Heparin containing cells were stained with alcian blue at pH 2.2, and counted by an automated technique (Technicon H6000). The cells were challenged with the specific antigen (ovalbumin), with antisera to guinea-pig IgG (non-subclass specific), IgG1 and IgG2, and the calcium ionophore A23187. Histamine release was measured by an automated spectrofluorometric technique, and leukotriene C4 was measured by radioimmunoassay. All of the following parameters were higher in the atrial than in ventricular cells (mean ratio and SEM of atrial: ventricular mast cell parameters in parenthesis): Histamine content/g wet tissues (3.32 +/- 0.71:1) (p less than 0.05), Absolute mast cell number as a proportion of total cell count (3.75 +/- 1.64:1), Histamine release induced by antigen (significant in one out of four experiments), anti-IgG (significant in three out of four experiments), anti-IgG1 (significant in two out of four experiments), and anti-IgG2 (higher but not statistically significant). Ionophore A23187 gave an inconsistent histamine release pattern: significantly higher release from atria in five treatments (different concentrations in different experiments), and higher ventricular release in three. Significantly more leukotriene C4 was released by antigen and the ionophore A23187 (mean of 3-5 treatments), but not with anti-IgG.
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PMID:Comparison of the response of mast cells in guinea-pig cardiac atria and ventricles. 243 72

Tryptase was previously shown to undergo rapid inactivation under physiological conditions unless stabilized by the presence of heparin. The current study shows that increasing the concentration of free tryptase enhances the preservation of enzymic activity, consistent with dissociation of the tetramer, rather than autodegradation, as the mechanism of inactivation. Heparin glycosaminoglycan fragments of Mr greater than 5700 are necessary for complete stabilization of tryptase activity. This stabilizing effect depends upon negative charge density rather than carbohydrate composition. Thus, keratan sulphate or hyaluronic acid were no better than physiological buffer alone; chondroitin monosulphates and heparan sulphate each prolonged the t1/2 about 20-fold over buffer alone; chondroitin sulphate E prolonged the t1/2 69-fold; and dextran sulphate and heparin provided complete stabilization of tryptase activity for 120 min. Poly-D-glutamic acid prolonged the t1/2 55-fold. In each case the loss of tryptase activity followed apparent first-order kinetics. Increasing the NaCl concentration from 0.01 M to 1.0 M increased the stability of free tryptase. In contrast, increasing the NaCl concentration in the presence of stabilizing polysaccharides decreased the stability of tryptase until dissociation of tryptase from each polysaccharide presumably occurred; thereafter tryptase stability increased as did that of free tryptase. The effect of salt concentration on heparin-stabilized tryptase activity (as opposed to stability) was also evaluated. The mast cell proteoglycans heparin and chondroitin sulphate E, by virtue of containing the naturally occurring glycosaminoglycans of highest negative charge density, may play a major role in the regulation of mast cell tryptase activity in vivo.
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PMID:Regulation of human mast cell tryptase. Effects of enzyme concentration, ionic strength and the structure and negative charge density of polysaccharides. 244 72

Mast cell population was studied in rats with experimental atherosclerosis. It has been established that animals kept for 8 months on atherogenic diet revealed marked changes in mast cell population. Predominance of light cells and cell defects were noted. Heparin saturation index was reduced (0.35), as compared to the control (3.9). Stimulation of anticoagulation system by DIP-alpha-thrombin in such animals revealed no heparin in the blood. Mast cell subpopulation was characterized by light cell predominance and low heparin saturation index. The nature of cell degradation remained unchanged. The data obtained indicate the defects in mast cell pool in animals with experimental atherosclerosis.
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PMID:[Mast cell population in rats with experimental atherosclerosis]. 382 23

Repopulation and maturation of rat mesenteric and peritoneal mast cells were studied after mast cell depletion by intraperitoneal injection of distilled water. Immature mast cells were first identified in the mesentery and peritoneal fluid 5 and 6 days, respectively, after water injection. The most immature mast cells that could be identified contained a few orthochromatic granules. Upon maturation, the granules became metachromatic and increased in size and number. Heparin, revealed by toluidine blue staining and berberine sulfate fluorescence, appeared simultaneously with orthophthaldialdehyde (OPT)-induced histamine fluorescence. Paraformaldehyde-induced serotonin fluorescence appeared somewhat later. Repopulation of mesentery and peritoneal fluid by mast cells seemed to be independent of each other and to occur from undifferentiated precursor cells.
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PMID:Maturation of adult rat peritoneal and mesenteric mast cells. A morphological and histofluorescence study. 395 36

We compared the relative capacities of two over-sulfated glycosaminoglycans, heparin and chondroitin sulfate E, to alter the function of native properdin (nP) and activated properdin (aP) in the formation and stabilization of the amplification C3 convertase (C3b,Bb). Heparin was more active on a weight basis than chondroitin sulfate E in inhibiting the formation of C3b,Bb without or with nP, but had no influence on the decay of a pre-formed convertase, either unstabilized or stabilized with nP or aP. In contrast, chondroitin sulfate E was over 10-fold more active than heparin in preventing the formation of C3b,Bb in the presence of aP, and gave dose-related acceleration of decay of pre-formed C3b,Bb,aP but not of unstabilized or nP-stabilized pre-formed convertase. The inhibitory effect of both glycosaminoglycans on the formation of C3b,Bb in the presence of nP or aP was less when the number of C3b sites per target cell was increased. The preferential action of chondroitin sulfate E on the function of aP during the formation and decay of C3b,Bb,aP as compared to C3b,Bb,nP implies functional differences in the two forms of P even when they have been incorporated into C3b,Bb. The equal potency, when adjusted for uronic acid content, of chondroitin sulfate E proteoglycan isolated from the T cell-dependent, bone marrow-derived murine mast cell and of chondroitin sulfate E glycosaminoglycan from squid reveals that the linkage of the glycosaminoglycan to a peptide core does not diminish its regulatory action on the alternative complement pathway.
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PMID:Inhibition of the function of activated properdin by squid chondroitin sulfate E glycosaminoglycan and murine bone marrow-derived mast cell chondroitin sulfate E proteoglycan. 642 31

Stimulation of the anticoagulation system with the structural analogs of alpha-thrombin, DPP-alpha-thrombin and prothrombin I having no proteolytic activity leads, as is the case with alpha-thrombin, to a decrease in the heparin content in mast cells and to a concurrent rise in the blood level of the complex compounds of heparin and blood proteins. Morphometry disclosed a substantial shift of mast cell population towards the light, heparin-free forms. In the experimental animals, the index of mast cell saturation with heparin dropped below one. Heparin release by mast cells proceeded by the merocrine secretion type, largely at the expense of granulolysis, with the cell integrity being preserved. Degranulation was effected via the strong form. Intravenous injection to the animals of alpha-thrombin in the presence of the anticoagulation system blockade with chlorpromazine produced no similar changes in the mast cell population.
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PMID:[Analysis of the mast cell population in excitation and blockade of the anticoagulant system]. 711 21

Migration of capillary endothelial cells is an important component of angiogenesis in vivo. Increased numbers of mast cells have been associated with several types of angiogenesis. We have used a quantitative assay in vitro to demonstrate that mast cells release a factor that significantly increases bovine capillary endothelial cell migration. The factor is present in medium conditioned by mast cells as well as lysates of mast cells. The stimulatory effect of mast cells on migration is specific for capillary endothelial cells. Furthermore, mast cells have no mitogenic activity for capillary endothelial cells. Of all the secretory products of mast cells tested, only heparin stimulated capillary endothelial cell migration in vitro. Heparin preparations from a variety of sources stimulated capillary endothelial cell migration to the same degree but did not stimulate migration of several other cell types. The migration activity of heparin and mast cell conditioned medium was blocked by specific antagonists of heparin (protamine and heparinase), but not by chondroitinase ABC. The migration activity of mast cell conditioned medium was resistant to heat (100 degrees C) and incubation with proteolytic enzymes. These results suggest that the role of mast cells in angiogenesis may be to enhance migration of the endothelial cells of growing capillaries.
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PMID:Mast cell heparin stimulates migration of capillary endothelial cells in vitro. 742 25

Rat mast cell protease 1 (RMCP-1) is a chymotrypsin-like serine protease (chymase) that is specifically expressed by connective-tissue-type mast cells. It is stored in the secretory granules of the cells in a complex with heparin proteoglycan, and the chymase/heparin proteoglycan complexes are released following mast cell activation. The present study was undertaken to examine if the association with heparin proteoglycan influenced the regulation of RMCP-1 by various macromolecular protease inhibitors. Endogenous mast cell heparin proteoglycan was shown to significantly block the inhibition of RMCP-1 by the serpins alpha 1-protease inhibitor and alpha 1-antichymotrypsin, as well as the inhibition by alpha 2-macroglobulin, soybean trypsin inhibitor and plasma. The blocking of protease inhibition showed an optimum at a RMCP-1/proteoglycan ratio of 5:1 (by mass), corresponding to approximately 80 RMCP-1 molecules bound/proteoglycan molecule. Chymase activity present on intact peritoneal mast cells, i.e. present in its native complex with heparin proteoglycan, was also shown to be largely resistant to inhibition by alpha 1-antichymotrypsin and alpha 1-protease inhibitor. Heparin 10-saccharides and 20-saccharides were inefficient in preventing the interaction of RMCP-1 with alpha 1-antichymotrypsin, whereas pig mucosal heparin (approximately 50 monosaccharide units) blocked protease inhibition. We have previously shown that heparin potentiates the catalytic activity of RMCP-1 and, in the present study, we show that the mechanism for chymase activation involves a sixfold reduction of the Km,app value of RMCP-1 for the chromogenic substrate S-2586. Thus, the association of mast cell chymase with heparin proteoglycan may serve both to potentiate the catalytic activity of the enzyme and to increase the life-span of the chymases by preventing their inhibition after exocytosis.
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PMID:Regulation of rat mast cell protease 1 activity. Protease inhibition is prevented by heparin proteoglycan. 758 46

Chymase, the major chymotryptic proteinase of human mast cells, can be released in substantial quantities following mast cell activation. As this enzyme is stored in the secretory granules in its fully active form, we have investigated various factors which might regulate its activity in storage and upon release. Chymase was purified from human skin by high salt extraction, cetylpyridinium chloride precipitation, heparin agarose affinity chromatography and gel filtration. Neither the addition of Mg2+ or Ca2+ (0.3-10 mM) nor their sequestration by EDTA had any effect on the rate of cleavage of the synthetic substrate N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide. Monovalent cations (Na+,K+) enhanced enzyme activity, but only at non-physiological concentrations (0.5-3.0 M), suggesting an ionic strength effect. At constant I = 0.15, enzyme activity was strongly pH-dependent: at pH 5.5 (the approximate pH of the mast cell granule) the activity was only 10% of that at pH 7.5 (the approximate pH of the extracellular space). Heparin, which is stored with chymase in the mast cell granule, accentuated this difference by enhancing activity at pH 7.5 by 33% and depressing it a pH 5.5 by 40%. Histamine at concentrations up to 50 mM (I = 0.15) had little effect on chymase activity at either pH, although high concentrations did attenuate the actions of heparin. It is concluded that pH and the interaction with heparin are central to the regulation of chymase activity within the granule and following release.
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PMID:Regulation of the activity of human chymase during storage and release from mast cells: the contributions of inorganic cations, pH, heparin and histamine. 761 63

To determine the role of heparin in mast cell exocytosis, we studied the effect of heparin on histamine release induced by compound 48/80 or calcium ionophore A23187 in canine mastocytoma cells (BR). Heparin caused concentration-dependent inhibition of compound 48/80-induced histamine release from mast cells (n = 4; P < 0.05) with a mean inhibitory concentration of 0.14 +/- 0.01 U/ml (mean +/- SE). Mean maximal inhibition was 69.3 +/- 2.0%. In contrast, heparin had no effect on calcium ionophore A23187-induced histamine release. Although benzyl alcohol, a preservative of pharmaceutical heparin, had no effect, purified heparin produced a similar inhibitory effect on compound 48/80-induced histamine release (n = 4; P < 0.05). The inhibitory effect of heparin on histamine release was rapid and was eliminated by washing cells. Dextran sulfate, a polysaccharide with negative charge density, produced a similar inhibitory effect on compound 48/80-induced histamine release (n = 4; P < 0.05). We conclude that heparin inhibits compound 48/80-induced exocytosis in mast cells probably by its negative charge density.
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PMID:Heparin inhibits histamine release from canine mast cells. 768 86


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