Granulocyte activation by endotoxin. I. Correlation between adherence and other granulocyte functions, and role of endotoxin structure on biologic activity.

Abstract

Reminiscent of high concentrations of formylated chemotactic peptides, another group of bacteria-derived products, the lipopolysaccharides and lipid A, stimulate PMN adherence to petri dishes. Attachment and spreading of PMN is accompanied by intense release of secondary granule constituents and marked stimulation of the hexose monophosphate shunt activity. Dose-response studies with endotoxin preparations of diverse activity show that induction of PMN adherence, enzyme release, and respiratory burst activation are highly correlated, suggesting that this functional triad is mediated by a common mechanism. Hyperadhesiveness inducing concentrations of the chemotactically inert endotoxin lead to marked inhibition of PMN migration without affecting the direction-finding mechanism of the cell toward formylated peptides and C-derived chemotaxin(s). Endotoxin preparations at a lower grade of aggregation are more active, and the polysaccharide chains of the molecule are not essential with respect to PMN stimulation. Under our experimental conditions, endotoxin-induced stimulation of PMN is not inhibited by indomethacin, suggesting independence of cyclooxygenase-derived products. This type of PMN activation may play an important role in endotoxin-mediated tissue damage in vivo. Furthermore, hyperadhesion-induced inhibition of PMN migration to inflammatory sites during endotoxemia might hamper host resistance.