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 protein ase in acute allergic reactions. We have purified chymase from human s kin tissue, and have investigated its potential to induce microvascula r leakage in vivo. Injection of chymase into the skin of guinea pigs p rovoked an increase in microvascular leakage within 20 min. Although s kin reactions were smaller than those elicited with similar quantities of histamine at this time point, they were much longer-lived, and wer e still apparent 120 min following injection. Chymase induced microvas cular 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 synergisti c interactions between chymase and either histamine or tryptase. Antih istamine pretreatment of animals did not reduce the magnitude of skin reactions to chymase suggesting that they were not mediated by histami ne release. Chymase could contribute to increases in microvascular per meability following mast cell degranulation in allergic disease. (C) 1 998 Elsevier Science B.V. All rights reserved.