PALMITIC ACID ANILIDE-INDUCED RESPIRATORY BURST IN HUMAN POLYMORPHONUCLEAR LEUKOCYTES IS INHIBITED BY A PROTEIN-KINASE-C INHIBITOR, RO-31-8220

Human polymorphonuclear leukocytes (PMNL) were exposed to palmitic aci d anilide, an impurity in the case oils that caused the Spanish Toxic Oil Syndrome in 1981, and to the corresponding fatty acid, palmitic ac id. The effects of these compounds were studied on the production of r eactive oxygen metabolites (ROM) and changes in the levels of free int racellular calcium. Palmitic acid anilide induced the production of re active oxygen metabolites in PMNL. Interestingly, the palmitic acid an ilide-induced respiratory burst was completely blocked by a protein ki nase C inhibitor, Ro 31-8220. Moreover, palmitic acid anilide additive ly amplified the production of ROM caused by a chemotactic peptide, fo rmyl-Methionyl-leucyl-Phenylalanine (FMLP). In contrast, palmitic acid anilide did not have any effect on the production of ROM induced by a tumor promoter, phorbol myristate acetate (PMA). Palmitic acid, in tu rn, did not markedly induce the production of ROM nor did it amplify t he agonist-induced respiratory burst. Neither of the compounds, alone or in combination with FMLP, affected the levels of intracellular calc ium in PMNL. These results indicate that the aniline moiety in palmiti c acid modifies its effects on the activation of human PMNL, and the s ubsequent oxidative burst. The present results also suggest that palmi tic acid anilide may activate PMNL through a protein kinase C-dependen t mechanism. (C) 1997 Elsevier Science Inc.