The Effect of Prostacyclin Mimetics on Neutrophil Function

Abstract

Prostaglandins such as PGE, and PGE₂ modulate a wide range of inflammatory and immunological processes. For example, PGE₂ can inhibit N-4-formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated neutrophil chemotaxis, aggregation, respiratory burst, enzyme release and phagocytosis (Schrör and Hecker, 1986; Wheeldon and Vardey, 1993; Wise and Jones, 1994). The inhibitory activity of PGE₂ on neutrophils appears to be mediated by an EP2, or an EP2-like receptor (Wheeldon and Vardey, 1993; Wise and Jones, 1994). Prostaglandins such as PGD₂ and PGI₂, but not PGF_2α or the thromboxane A₂ mimetic U46619, also inhibit neutrophil function with PGE₂ and PGD₂ being more important in human neutrophils (Wheeldon and Vardey, 1993) and PGE₂ and PGI₂ being involved in rat neutrophils (Wise and Jones, 1994). EP2-, DP- and IP-receptors are all coupled to the production of cyclic AMP (Coleman et al., 1994); this observation taken together with the knowledge that cyclic AMP mimetics are also inhibitors of neutrophil function tends to support the hypothesis that cyclic AMP mediates the inhibitory activity of these prostaglandin receptors.