Inhibition by Leukotriene B5 of Leukotriene B4-Induced Activation of Human Keratinocytes and Neutrophils

Abstract

Leukotriene B5 (LTB5) that is generated enzymatically from eicosapentaenoic acid (EPA), was compared with arachidonic acid-derived LTB4 for its DNA synthetic effect on cultured human epidermal keratinocytes and for its chemokinetic effect on human blood neutrophils. Leukotriene B5 was much less potent than LTB4 in stimulating DNA synthesis and in inducing chemokinesis. Furthermore, the maximum response to LTB5 was only a mean of 38% that of LTB4 for mitogenesis and 70% that of LTB4 for chemokinesis. At an optimally active concentration of LTB4 (10(-10) M) the addition of LTB5 suppressed the enhancement by LTB4 of DNA synthesis in keratinocytes by a mean of 21%, 33%, and 54%, respectively, at 10(-9) M, 10(-8) M, and 10(-7) M LTB5. Leukotriene B5 inhibited to a lesser extent the maximum neutrophil chemokinetic response elicited by 10(-10) M LTB4 with mean inhibition of 10%, 20%, and 18%, respectively, by 10(-9) M, 10(-8) M, 10(-7) M LTB5; LTB5 was without effects on N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-elicited neutrophil chemokinesis and on thrombin-stimulated keratinocyte DNA synthesis. The dietary introduction of n-3 fatty acids, such as EPA, may reduce the epidermopoiesis and neutrophil migration evoked by LTB4 through decreases in generation of LTB4 and the capacity of LTB5 to inhibit the effects of LTB4.