NEUTROPHIL MIGRATION-INHIBITORY PROPERTIES OF POLYUNSATURATED FATTY-ACIDS - THE ROLE OF FATTY-ACID STRUCTURE, METABOLISM, AND POSSIBLE 2ND MESSENGER SYSTEMS

The n-3 polyunsaturated fatty acids (PUFA) appear to have antiinflamma tory properties that can be partly explained by their biological activ ity on leukocytes. Since leukocyte emigration is an essential componen t of the inflammatory response, we have examined the effects of the n- 3 PUFA (eicosapentaenoic and docosahexaenoic acids) on neutrophil rand om and chemotactic movement. Preexposure of neutrophils for 15-30 min to 1-10 mu g/ml PUFA reduced the random and chemotactic migration to b oth FMLP- and fungi-activated complement. The inhibitory effect dimini shed with increasing saturation and carbon chain length, and methylati on abolished this activity. Arachidonic and docosahexaenoic acids were the most active fatty acids. The PUFA concentration required to inhib it migration was dependent on cell number, suggesting that the fatty a cid effects on leukocyte migration in vivo may be governed by the stag e of the inflammatory response. It was concluded that the PUFA rather then their metabolites were responsible for the inhibition since: (a) antioxidants did not prevent the PUFA-induced migration inhibition and the hydroxylated intermediates were less active, and (b) inhibitors o f the cyclooxygenase and lipoxygenase pathways were without effect. In hibitors of protein kinases and calmodulin-dependent enzyme system did not prevent the PUFA-induced migration inhibition, which was also ind ependent of phospholipase D-catalyzed hydrolysis of phospholipids. It is also shown that PUFA decrease the FMLP-induced Ca2+ mobilization.