The induction of a prolonged increase in microvascular permeability by human mast cell chymase.
Chymase is a major constituent of the secretory granules of human mast cells, but little is known of the contribution of this serine proteinase in acute allergic reactions. We have purified chymase from human skin tissue, and have investigated its potential to induce microvascular leakage in vivo. Injection of chymase into the skin of guinea pigs provoked an increase in microvascular leakage within 20 min. Although skin reactions were smaller than those elicited with similar quantities of histamine at this time point, they were much longer-lived, and were still apparent 120 min following injection. Chymase induced microvascular leakage was reduced in the presence of soybean trypsin inhibitor, and abolished by heat inactivating the enzyme, indicating dependence on an intact catalytic site. Little evidence was found for synergistic interactions between chymase and either histamine or tryptase. Antihistamine pretreatment of animals did not reduce the magnitude of skin reactions to chymase suggesting that they were not mediated by histamine release. Chymase could contribute to increases in microvascular permeability following mast cell degranulation in allergic disease.
Immunopharmacology, Group, Southampton General Hospital, UK.
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D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002384:Catalysis; D053818:Chymases; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D008407:Mast Cells / Q000201:enzymology*; D012697:Serine Endopeptidases / Q000302:isolation & purification / Q000494:pharmacology*
D006634:Histamine H1 Antagonists; D012697:Serine Endopeptidases; D053818:Chymases