Modulation of acute immune complex-mediated tissue injury by the presence of polyionic substances

Abstract

Considerable attention has been focused on the role of electrostatic charge in the pathogenesis of immune complex-mediated tissue injury. The authors have examined the ability of cationic (histone, polyhistidine, polyarginine) and anionic (polyanetholsulfonate) polyelectrolytes to modulate acute immune complex-mediated tissue injury. Tissue injury elicited in rats by the reversed dermal Arthus reaction was increased 26-43% by addition of polyelectrolytes to antibody prior to its intradermal injection. Kinetic studies using 111In-labeled neutrophils indicated that the enhanced tissue injury was not the result of increased influx of neutrophils. Infusion of polyethylene glycol-conjugated superoxide dismutase prior to induction of the Arthus reaction resulted in 40-68% suppression of tissue injury. Concomitant in vitro functional studies (enzyme secretion, O-2 and H2O2 generation, and chemiluminescence) of rat neutrophils demonstrated that addition of polyelectrolytes to preformed immune complexes (IgG-bovine serum albumin) resulted in marked increases in O-2, H2O2, and chemiluminescence, but no increases in enzyme secretion, compared with neutrophils stimulated with immune complexes alone. The cationic polyelectrolytes did not alter the capacity of preformed immune complexes to activate complement in vitro. These studies suggest that both cationic and anionic polyelectrolytes can increase the pathogenic potential of immune complexes and that this modulation is, at least in part, mediated by enhanced generation of toxic oxygen-derived metabolites by neutrophils.