EFFECTS OF LIPOXIN-A, ON CHEMOTAXIS AND DEGRANULATION OF HUMAN EOSINOPHILS STIMULATED BY PLATELET-ACTIVATING-FACTOR AND N-FORMYL-L-METHIONYL-L-LEUCYL-L-PHENYLALANINE

Lipoxins are trihydroxytetraene metabolites derived through a double lipoxygenation of arachidonic acid. Lipoxin A(4) (LXA(4)) was prepared by total chemical synthesis, and its capacity to modulate eosinophil migration has been evaluated. LXA(4) 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 LXA(4) (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 LXA(4) which produced 50% inhibition (IC50) of eosinophil migration was approximately 10(-6) M. LXA(4) (10(-10)-10(-6) M) did not elicit ECP release or modulate ECP release induced by 10(-6) M FMLP. LXA(4) may have antiallergic properties in preventing eosinophilic migration.