Biochemical characteristics of ATP-induced secretion of lysosomal enzymes from rabbit polymorphonuclear leukocytes

Abstract

ATP induces a release of the lysosomal enzymes,β-glucuronidase and lysozyme, but not the cytoplasmic marker, lactic dehydrogenase, from rabbit peritoneal polymorphonuclear leukocytes. The release requires a low-ionic-strength medium but not divalent cations. It occurs to a greater extent in the presence of K⁺ than Na⁺, is greatly enhanced by cytochalasin B, is temperature dependent, and apparently requires a source of metabolic energy as indicated by its inhibition by deoxyglucose. The release is also inhibited by iodoacetate and the organic mercurial, salyrgan. DFP does not inhibit the release, indicating that esterase activation apparently is not involved. ADP and AMP do not sustain the release, nor do the ATP phosphorate analogs in which a methylene group is substituted for the oxygen between theα andβ phosphate groups or theβ andγ phosphates.

A tentative explanation for these findings is that ATP induces lysosomal enzyme release in polymorphonuclear leukocytes by reacting directly with an ATPase which needs low ionic strength but not divalent cations for its activity. In doing so, ATP bypasses the proesterase activation and external Ca²⁺-mediated steps required in other forms of induced lysosomal enzyme release in the polymorphonuclear leukocyte but uses the same common final pathway.