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.