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, 80 (14), 4349-53

Inhibition by Prostaglandins of Leukotriene B4 Release From Activated Neutrophils

Inhibition by Prostaglandins of Leukotriene B4 Release From Activated Neutrophils

E A Ham et al. Proc Natl Acad Sci U S A.

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 E1 and E2 (PGE1 and PGE2) inhibit LTB4 release from PMN in a dose-related manner with an IC50 of 1 X 10(-8) M. This action is associated with increased levels of cyclic AMP. The inhibitory activity of a variety of PGs 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. In contrast, lysosomal enzyme release is only minimally affected by physiological levels of PGs. These data are consistent with an action of PGs at the level of the PG receptor on LTB4 and O2- release from the fMet-Leu-Phe-stimulated rat peritoneal PMN. In addition, the fMet-Leu-Phe-induced adherence of PMN to endothelial cells and inhibition of this phenomenon by PGs may now be explained by PG-mediated inhibition of LTB4 formation.

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