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)

Phosphatidylserine (PtdSer) potentiates histamine secretion from mast cells exposed to concanavalin A and Ca2+. In order to identify the form of PtdSer that is responsible for its effect on mast cell secretion, PtdSer containing a tritium-labeled serine moiety (3H-PtdSer) was synthesized from egg yolk phosphatidylcholine. The critical micelle concentration (CMC) of 3H-PtdSer and the binding isotherm for 3H-PtdSer interaction with mast cells were determined. The midpoints of the binding isotherm and the dose-response curve for potentiation of secretion coincide and are 2 orders of magnitude greater than the CMC. The shape of the binding curve is explicable either in terms of simple binding of preformed PtdSer micelles or of cooperative binding of monomeric PtdSer in which the number of molecules cooperatively associating with a mast cell binding site is equal to the number of monomers in a PtdSer micelle. In either case, at equilibrium, PtdSer micelles are bound to the mast cells. The number of PtdSer molecules bound to a single mast cell at equilibrium was estimated to be 3.7 X 10(9).
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PMID:Interaction of phosphatidylserine with mast cells. 8 84

Guinea pig lung mast cells and blood basophils were isolated and purified and their mediator release characteristics were compared. Upon stimulation with the antigen ovalbumin (OA) of cells passively sensitized with antiovalbumin (anti-OA) antibody, both cell types released histamine. The sensitivity and maximal response (20 to 25% histamine release) to OA was similar for both cells and was unaffected by cell purification. Antigen-induced histamine release (HR) was dependent upon added calcium to a similar extent (1 mM Ca++ maximal release) in both cell types; OA stimulation of passively sensitized mast cells also released leukotriene bioactivity (maximal release, 52 +/- 7 units/10(6) mast cells). There was no correlation between OA-induced leukotriene release and mast cell purity. No leukotriene bioactivity was detected in actively (sheep blood sensitization) or passively (anti-OA) sensitized basophils. Both lung mast cells and blood basophils released histamine in response to the secretagogues calcium ionophore A23187 and 12-O-tetradecanoylphorbol-13-acetate (TPA); TPA-induced HR from mast cells was independent of added calcium. In basophils, TPA-induced HR was only partially independent of added calcium. While both cell types were poorly responsive to the secretagogue 48/80, only the lung mast cell demonstrated inconsistent HR to concanavalin A (Con-A). Phosphatidylserine had no effect on HR provoked by antigen, Con-A, or compound 48/80. These observations demonstrate similarities and differences in mediator release characteristics between guinea pig lung mast cells and blood basophils that are similar to those observed with human lung mast cells and basophils. These observations also suggest a lack of influence on mediator release by other cell types present in dispersed lung cell and mixed leukocyte preparations.
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PMID:Comparative studies of mediator release from guinea pig lung mast cells and basophils. 242 92

The hypothesis of this study is summarized in Fig. 6. Phosphatidylserine due to distribution in the internal side of plasma membrane is prevented to react with the extracellular environment. When injury to cell occurs, phospholipid asymmetry is lost and the exposed phosphatidylserine becomes a signal of cell damage. Phosphatidylserine may activate defense reactions while it is still anchored to plasma membrane (Zwaal, 1978; Tanaka and Schroit, 1983). Alternatively, the soluble lysophosphatidylserine is generated, ready to diffuse and transmit the information of tissue damage to other cells. In this sequence of events, lysophosphatidylserine becomes an autacoid, originated from a membrane phospholipid. In rodents, lysophosphatidylserine seems specifically devoted to activate mast cells. The role of these cells in the regulation of the immune reactions and in tissue repair has been advocated (Dexter et al., 1981). The lysophosphatidylserine-induced mast cell activation has been shown in vivo and in vitro in a variety of rodent species (mouse, rat, gerbil, hamster). It may occur through a direct effect or through the participation of synergistic endogenous compounds. Structure-activity relationships in the action of lysophosphatidylserine show that the effect on mast cells is linked to a definite molecular organization. Determinants of the mast cell activation are the free amino group and the carboxyl group of the serine. Support to the general hypothesis of this study originates from the observation that active lysophosphatidylserine is generated within a population of leukocytes, the cells migrating in areas of wounded tissue (Mietto et al., 1987). Production of lysophosphatidylserine can be anticipated in pathological situations associated with extensive cell death (tumor growth, graft rejection, burns). At present, the observations on lysophosphatidylserine are confined to rodent mast cells. Other histamine-secreting cells (e.g., the human basophil) are unresponsive to this phospholipid (Kolster et al., 1987). Among the endogenous compounds interacting with lysophosphatidylserine, nerve growth factor seems of particular interest (Bruni et al., 1982). The synergism with lysophosphatidylserine has been confirmed in other laboratories (Sugiyama et al., 1985; Pearce and Thompson, 1986; Mazurek et al., 1986). The concerted effects by these two compounds on mast cells is in line with current opinion on the participation of nerve growth factor in the regulation of inflammatory and immune reactions (Mietto et al., 1987; Weskamp and Otten, 1987).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Autacoid properties of lysophosphatidylserine. 307 95

The activity of chymase was markedly inhibited by phosphoglycerides such as phosphatidic acid, phosphatidylserine, and phosphatidylinositol, but was not affected by acylglycerides, phosphoglyceroserine, serine, inositol, or glycerol. These results suggest that both the nonpolar hydrophobic hydrocarbon tails and the polar hydrophilic head are essential for the inhibitory effects of phosphoglycerides. Binding of a primary amine to an anionic polar head of phosphatidic acid, such as in phosphatidylserine and phosphatidylethanolamine, slightly decreased the inhibitory effect of phosphatidic acid and, conversely, binding of a strong cation to the head, such as in phosphatidylcholine, resulted in its activation of chymase. Phosphatidic acid containing an unsaturated fatty acid, such as dioleoyl phosphatidic acid, caused the same extent of inhibition as natural phosphatidic acid from bovine brain, but was 20 times more inhibitory than phosphatidic acid containing a saturated fatty acid, such as distearoyl phosphatidic acid. The inhibition by phosphatidylserine was noncompetitive and pseudoirreversible, and the Ki value was 0.54 microM. The inhibition of chymase by phosphatidylserine was pH dependent, being strong at pH 8.5 to 9.5 but weak below pH 7.5. Phosphatidylserine specifically inhibited chymase and elastase; it did not inhibit the other chymotrypsin-type serine endopeptidases tested, trypsin, papain, collagenase, carboxypeptidase A, or cathepsin D.
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PMID:Inhibition of chymase activity by phosphoglycerides. 388 53

The mast cell degranulating capacity of neurotensin and three of its fragments was examined. In Tyrode solution (137 mM NaCl, 2.7 mM KCl, 0.4 mM NaH2PO4, 1.4 mM CaCl2, 1 mM MgCl2, 10 mM Hepes, 5.6 mM glucose, pH 7.4), neither intact neurotensin nor its C-terminal tripeptide (Tyr-Ile-Leu) caused any release of histamine. Concentrations of neurotensin exceeding 10(-4)M did cause histamine release but through lysis of the cells. The C-terminal hexa- and octapeptides of neurotensin (Arg-Arg-Pro-Tyr-Ile-Leu and Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu, respectively) induced a non-cytolytic release of histamine with the latter peptide being more active (ED50 = 90 microM for the hexapeptide and 13 microM for the octapeptide). This release was not affected by the C-terminal tripeptide. It was found to be calcium-dependent and was inhibited by the anti-allergic drug, disodium cromoglycate. Phosphatidylserine did not enhance release of histamine and saturation of the immunoglobulin E (IgE) receptors did not inhibit it.
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PMID:Structure-activity relationship in the mast cell degranulating capacity of neurotensin fragments. 618 72