Inhibition by prostaglandins of leukotriene B4 release from activated neutrophils.

Abstract

Chemoattractant N-formylmethionylleucylphenylalanine (fMet-Leu-Phe) in the presence of cytochalasin B stimulates the release of leukotriene B4 (LTB4), superoxide (O2-) and N-acetylglucosaminidase from elicited rat peritoneal and human peripheral neutrophils [PMN (polymorphonuclear leukocytes)]. Prostaglandins [PG]E1 and PGE2 inhibit LTB4 release from PMN in a dose-related manner with an IC50 [median inhibitory concentration] of 1 .times. 10-8 M. This action is associated with increased levels of cAMP. The inhibitory activity of a variety of PG on LTB4 production by rat peritoneal PMN parallels their affinity for PGE receptors in other tissues. O2- release is also suppressed by low levels of PGE1 and PGE2 in a dose-related manner and this inhibition is enhanced by theophylline. Lysosomal enzyme release is only minimally affected by physiological levels of PG. The data are consistent with an action of PG at the level of the PG receptor on LTB4 and O2- release from the fMet-Leu-Phe-stimulated rat peritoneal PMN. The fMet-Leu-Phe-induced adherence of PMN to endothelial cells and inhibition of this phenomenon by PG may not be explained by PG-mediated inhibition of LTB4 formation.