Cytotoxic enzyme release and oxygen centered radical formation in human neutrophils are selectively inhibited by E-type prostaglandins but not by PGI2

Summary The action of PGE₁, PGE₂, PGI₂ and iloprost on superoxide anion generation, lysosomal enzyme release, and changes of Ca²⁺ fluxes in human polymorphonuclear leukocytes (PMN) was studied in vitro. Both PGE-type compounds were equipotent inhibitors of FMLP-and PAF-stimulated superoxide anion generation, -glucuronidase release (IC₅₀ 3–5 mol/l) and Ca²⁺ influx while PGI₂ and iloprost were ineffective at concentrations up to 10 mol/l. These inhibitory actions of PGE₁ and PGE₂ were paralleled by an increase in cAMP level of the PMN while no change occurred with PGI₂ and iloprost. None of the prostaglandins affected the initial intracellular Ca²⁺ liberation after challenge with FMLP or PAF. Preincubation of PMN with PGE₁ and PGE₂ but not with iloprost resulted in subsequent desensitization against a second administration of these compounds. None of the compounds affected PMN activation produced by arachidonic acid or calcimycin (A 23187).These data demonstrate that PGE-type compounds are effective inhibitors of receptor-mediated (PAF, FMLP) activation of human PMN while prostacyclins are considerably less potent. This suggests that the inhibitory prostaglandin receptor on human PMN belongs to the E-type being functionally different from the inhibitory prostaglandin receptor on human platelets. These results suggest that compounds, such as PGE₁ and PGE₂ might be superior to prostacyclins to prevent PMN-associated generation of reactive oxygen species and lysosomal enzyme release in situations with endogenous PMN activation, i. e. inflammatory reactions.Send offprint requests to K. Schrör at the above address