Human mast cell chymase induces the accumulation of neutrophils, eosinophils and other inflammatory cells in vivo

1 The roles of chymase in acute allergic responses are not clear, despite t he relative abundance of this serine proteinase in the secretory granules o f human mast cells. We have isolated chymase to high purity from human skin tissue by heparin-agarose affinity chromatography and Sephacryl S-200 gel filtration procedures, and have investigated the ability of human mast cell chymase to stimulate cell accumulation following injection into laboratory animals. 2 Injection of chymase provoked marked neutrophilia and eosinophilia in the skin of Dunkin Hartley guinea-pigs. Compared with saline injected control animals, there were some 60 fold more neutrophils and 12 fold more eosinoph ils present at the injection site. 3 Following injection of chymase into the peritoneum of BALB/c mice, there were up to 700 fold more neutrophils, 21 fold more eosinophils, 19 fold mor e lymphocytes and 7 fold more macrophages recovered than from saline inject ed controls at 16 h. Doses of chymase as low as 5 ng (1.7 x 10(-13) mole) s timulated an inflammatory infiltrate, and significant neutrophilia was elic ited within 3 h. 4 The chymase induced cell accumulation in both the guinea-pig and mouse mo dels was dependent on an intact catalytic site, being reduced by co-injecti on of proteinase inhibitors or heat inactivation of the enzyme. 5 Go-injection of histamine or heparin significantly reduced the chymase in duced neutrophil accumulation, whereas neither histamine nor heparin by the mselves had any effect on the accumulation of nucleated cells. No synergist ic or antagonist interactions between chymase and tryptase were observed wh en these two major mast cell proteinases were co-injected into the mouse pe ritoneum. 6 Our findings suggest that chymase may provide an potent stimulus for infl ammatory cell recruitment following mast cell activation.