In vivo chemotaxis of bovine neutrophils induced by 5-lipoxygenase metabolites of arachidonic and eicosapentaenoic acid.

The 5-lipoxygenase metabolites of arachidonic (AA) and eicosapentaenoic acid (EPA), 5S,12R-dihydroxy-6,8,10,14-eicosatetraenoic acid (LTB4), 5-hydroxyeicosatetraenoic acid (5-HETE), 5S,12R-dihydroxy-6,8,10,14,17-eicosapentaenoic acid (LTB5), and 5-hydroxyeicosapentaenoic acid (5-HEPE), were injected intradermally into the ear skin of steers to assess their in vivo potency as chemotactic factors for bovine neutrophils. A dose of 30 picomoles of LTB4 was required to elicit a significant extravascular dermal accumulation of neutrophils (P less than 0.05). In contrast, 1.0 nanomole of LTB5 was required to achieve a cellular influx equivalent to that elicited by 30 picomoles of LTB4. Nearly five times as many neutrophils were present in the bovine dermis injected with 1.0 nanomole of LTB4 compared with sites given the equivalent dose of LTB5 (245 cells/sq mm vs. 52 cells/sq mm). Six nanomoles of either 5-HETE or 5-HEPE were required before a significant neutrophil accumulation occurred. These results show clearly that 5-lipoxygenase metabolites can initiate the extravascular accumulation of bovine neutrophils in vivo. However, the chemotactic potency of the EPA metabolites is much reduced when compared with that of the homologous AA lipids. The results obtained support the premise that modification of the inflammatory response, including control of cellular influxes, by dietary supplementation with EPA is feasible.