Interaction of group A streptococcal peptidoglycan polysaccharide with human polymorphonuclear leukocytes: implications for pathogenesis of chronic inflammation

Abstract

Injection of sterile aqueous preparations of the peptidoglycan polysaccharide of group A streptococci produces chronic inflammation in several animal models. Accordingly, the effect of peptidoglycan and group A-specific polysaccharide (PG-APS) polymers on human polymorphonuclear neutrophil oxidative metabolism was studied with the supposition that this interaction may contribute to the inflammation observed. PG-APS in concentrations of 1.0 to 100 micrograms/ml stimulated oxygen consumption and hexose monophosphate shunt activity in the presence of 10% normal serum in a dose-related manner. Stimulation did not occur in serum-free media and was reduced in media with heat-treated serum. The stimulation of hexose monophosphate shunt activity by PG-APS opsonized with normal serum (bound complement components) and the activated supernatant from which PG-APS had been removed by centrifugation (presumably containing the soluble complement component, C5a) demonstrated 79 and 75%, respectively, of the stimulation with PG-APS in the presence of 10% normal serum. PG-APS triggered release of O2- (3.4 +/- 2.0 nmol by 10(6) human polymorphonuclear neutrophils over 30 min), which was significantly enhanced (9.6 +/- 2.9 nmol O2-) by treatment of cells with cytochalasin B. These results show that PG-APS interacts with serum in such a fashion as to activate human polymorphonuclear neutrophil metabolism and increase secretion of O2-.