title: Complement and immunoglobulins stimulate superoxide production by human leukocytes independently of phagocytosis.
abstract: Human peripheral blood polymorphonuclear leukocytes, when exposed to appropriate stimuli, generate significant amounts of superoxide anion (O-.2), a highly reactive molecule which is possibly involved in bacterial killing. Since the subcellular localization and mechanism of activation of O-.2 generating systems are unknown, we have investigated superoxide dismutase-inhibitable cytochrome c reduction (attributable to O-.2) by, and lysosomal enzyme release from, normal polymorphonuclear leukocytes and cells rendered incapable of ingesting particles by treatment with cytochalasin B. Neither phagocytosis nor lysosomal degranulation were prerequisites for enhanced O-.2 generation. Cytochalasin B-treated cells exposed to (a) serum-treated zymosan, a C3b receptor stimulus; (b) heat aggregated human IgG, an Fc receptor stimulus; and (c) the complement component, C5a, generated enhanced amounts of O-.2 in a time and concentration-dependent fashion. These cells also responded by releasing lysosomal enzymes, but there was no correlation between the ability of any immune reactant to provoke enzyme release and its ability to stimulate O-.2 generation. The three stimuli also enhanced O-.2 generation by normal (untreated) polymorphonuclear leukocytes, but only serum-treated zymosan and aggregated IgG were capable of provoking lysosomal enzyme release from normal cells. Untreated zymosan and native IgG neither stimulated O-.2 production nor provoked lysomal enzyme release. Since enhanced O-.2 production was stimulated by immune reactants in the absence of phagocytosis, the O-.2 generating system is very likely associated with the external plasma membrane of the polymorphonuclear leukocyte. Leukocyte membrane receptors for complement and immunoglobulins may therefore not only serve in particle recognition but also may initiate biochemical events which accompany phagocytosis and killing.
mesh_terms: D000328:Adult; D003176:Complement C3; D003165:Complement System Proteins; D006801:Humans; D007074:Immunoglobulin G; D066298:In Vitro Techniques; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism*; D010100:Oxygen / Q000096:biosynthesis*; D010587:Phagocytosis; D013481:Superoxides / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D003176:Complement C3; D007074:Immunoglobulin G; D013481:Superoxides; D003165:Complement System Proteins; D010100:Oxygen