Rat leukocytes from inflammatory peritoneal exudates respond in vitro to a variety of chemotactic and phagocytic stimuli by releasing both elastase and cathepsin G neutral proteinase enzyme activities. PAF, FMLP, and PMA stimulated a rapid, cytochalasin B-dependent, dose-related release of both enzymes; however, leukotriene B4 was inactive. It was not possible to measure the activity of zymosan-activated serum on these cells as rat serum contains high levels of proteinase inhibitors. The calcium ionophore A23187 stimulated a dose-related, time-dependent, cytochalasin B-independent enzyme release. Concanavalin A stimulated a weak, nondose-related release of enzyme activity. Zymosan and serum-coated zymosan stimulated enzyme secretion which was markedly inhibited by the presence of cytochalasin B. These data indicate that release of azurophillic granule neutral proteinases from rat inflammatory leukocytes can be detected and quantitated in vitro. This model could provide a test system for monitoring the pattern and specificity of enzyme release from azurophil granules. The ability of a variety of stimuli to induce proteolytic enzyme release from inflammatory neutrophils may be of considerable relevance to chronic inflammatory diseases.
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