12-Lipoxygenase product as an inhibitor of the action of chemoattractant peptide fMet-Leu-Phe in rat neutrophils.

1. 12-Hydroxyeicosatetraenoic acid (12-HETE) has been evaluated for its capacities to modulate neutrophil migration and cytosolic Ca2+ ([Ca2+]i) using compounds prepared by chemical synthesis and tissue extract from dog gingiva. 2. 12-HETE inhibited N-formyl-Met-Leu-Phe (fMLP)-stimulated neutrophil migration in a concentration-dependent fashion. 3. The tissue extract from dog gingiva mimicked the actions of 12-HETE. 4. Although 12-HETE failed to increase [Ca2+]i, preincubation of neutrophils with 12-HETE led to a suppression of [Ca2+]i when the cells were subsequently stimulated by fMLP. 5. Again tissue extract from dog gingiva mimicked the action of 12-HETE on [Ca2+]i. 6. These results suggest the possible correlation of the inhibitory activities of 12-HETE on the regulation of neutrophil migration and Ca2+ mobilization, and this may be important for the role of 12-HETE in pathogenesis in periodontal tissues.