Cellular serine proteinase induces chemotaxis by complement activation

Abstract

INFILTRATION of inflamed or injured tissues by polymorphonuclear leukocytes is a fundamental pathophysiological response. Undoubtedly, there are numerous mechanisms by which leukocytes are attracted to an area of damage. One possibility is that cellular injury could release or activate a proteolytic enzyme which could generate chemotactic factors. Extracts of parenchymatous tissues¹ and cells² are chemotactic when they are incubated with complement sufficient serum. Macrophages³ and leukocytes⁴ contain a proteinase which generates chemotactic peptides, and recently human polymorphonuclear leukocytes have been shown to secrete an enzyme which activates complement⁵. Lazarus and Barrett extracted and characterised a serine proteinase which induced polymorphonuclear leukocyte infiltration of the skin when injected intradermally⁶. Subsequently, this proteinase, which is both cytotoxic and phlogistic, has been purified to homogeneity from whole human skin⁷, human epidermis⁸, human lymphocytes⁹ and cultures of newborn mouse epithelium (G.S.L., unpublished). This report demonstrates that this proteinase is significantly more active than trypsin, plasmin or Pronase in generating polymorphonuclear leukocyte accumulation and that chemotactic activity is largely dependent on complement activation.