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. 1973 Oct;70(10):2916–2920. doi: 10.1073/pnas.70.10.2916

Mechanisms of Lysosomal Enzyme Release from Human Leukocytes: Microtubule Assembly and Membrane Fusion Induced by a Component of Complement

Ira Goldstein *, Sylvia Hoffstein *, John Gallin †, Gerald Weissmann *
PMCID: PMC427138  PMID: 4355374

Abstract

A low-molecular-weight component of complement, similar to or identical with human C5a, interacts with human polymorphonuclear leukocytes treated with cytochalasin B and provokes extracellular release of lysosomal enzymes from these cells. Enzyme release occurs in the absence of particles and is selective in that it is not accompained by release of cytoplasmic enzymes. Cell viability is not altered. Pharmacologic agents that regulate secretion of other inflammatory mediators influenced complement-dependent enzyme release: cAMP and theophylline, prostaglandin E1 and colchicine inhibited, whereas cGMP enhanced release of enzymes. Ultra-structural histochemistry of cells exposed to this component of complement revealed degranulation, fusion of lysosomal with plasma membranes, and transient assembly of microtubules associated with the release of endogenous myeloperoxidase. Our findings suggest that these intracellular events are common to two important responses of polymorphonuclear leukocytes in inflammation and tissue injury: (a) release of lysosomal hydrolases and (b) chemotaxis.

Keywords: C5a, chemotaxis, cytochalasin B, cAMP: cGMP antagonism

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