Evaluation of the role of oxygen radicals in polymorphonuclear leukocyte aggregation

Abstract

Oxygen radicals have been shown to alter granulocyte function by injury to the cell membrane or cytoskeleton. We have investigated the effect of such injury on the aggregation of granulocytes upon C5a or PMA stimulation. Granulocyte aggregation was not altered in the presence of the oxygen radical scavengers SOD, catalase, mannitol, or benzoate. To test whether oxygen radicals were required for aggregation, we evaluated three patients with chronic granulomatous disease of childhood. The response of PMNs from these patients was no different from controls. Hydrocortisone, an inhibitor of both granulocyte aggregation and oxygen radical generation, was then studied to decide whether its impairment of radical production contributed to its effect on aggregation. Five times the concentration of hydrocortisone needed to inhibit radical generation was required to impair aggregation by 50%. In addition, hydrocortisone was able to impair the aggregation of the PMNs of a patient with chronic granulomatous disease. These data suggest that oxidative injury to the cell membrane or cytoskeleton does not significantly contribute to the aggregation of granulocytes. In addition, inhibitors of aggregation, such as hydrocortisone, work through mechanisms other than by scavenging radicals.