Effects of lipoxin A4 on chemotaxis and degranulation of human eosinophils stimulated by platelet‐activating factor and N‐formyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanine

Abstract

Lipoxins are trihydroxytetraene metabolites derived through a double lipoxygenation of arachidonic acid. Lipoxin A₄ (LXA₄) was prepared by total chemical synthesis, and its capacity to modulate eosinophil migration has been evaluated. LXA₄ is a weak and partial chemotactic agent; at 10⁻⁶ M, it achieved about 20% of the response of 10⁻⁶ M platelet‐activating factor (PAF). Preincubation of eosinophils with increasing doses of LXA₄ (10⁻¹⁰−10⁻⁵ M) resulted in a concentration‐dependent inhibition of cell migration induced by 10^‐6 M formyl‐methionyl‐leucyl‐phenylalanine (FMLP) and 10^‐6 M PAF. The concentration of LXA₄ which produced 50% inhibition (IC₅₀) of eosinophil migration was approximately 10^‐6 M. LXA₄ (10^‐10‐10^‐6 M) did not elicit ECP release or modulate ECP release induced by 10^‐6 M FMLP. LXA₄ may have antiallergic properties in preventing eosinophilic migration.