Epidermal cell-polymorphonuclear leukocyte cooperation in the formation of leukotriene B4 by transcellular biosynthesis

Abstract

The cellular origin of Leukotriene B4, a potent pro-inflammatory agent that is present in psoriatic lesions, has not been completely ascertained. The present study was performed in order to assess the possible contribution of epidermal cells to leukotriene B4 synthesis through 5-lipoxygenase or by means of transcellular metabolism of the epoxide intermediate leukotriene A4 from activated polymorphonuclear leukocytes. The metabolism of exogenous arachidonic acid in fresh human epidermal cell, polymorphonuclear leukocyte or mixed suspensions was determined by means of high-performance liquid chromatography. Epidermal cells transformed arachidonic acid mainly into 12-hydroxy-eicosatetraenoic acid and prostaglandin E2. Formation of prostaglandins F2 alpha and D2, 12-hydroxy-eptadecatrienoic acid, and 15- and 11-hydroxy-eicosatetraenoic acids was also detected. We did not detect any eicosanoid derived from 5-lipoxygenase pathway. Mixed suspensions of polymorphonuclear leukocytes and epidermal cells (ratio 1:4) produced 1.72 times more leukotriene B4 than leukocytes alone under the same experimental conditions. Epidermal cells incubated with 5 microM authentic leukotriene A4 for 3 min yielded 2.954 +/- 0.27 pmoles/10(6) cells of leukotriene B4, which was characterized by co-elution with authentic standard and its ultraviolet absorption spectrum. These data demonstrate the existence of a leukotriene A4 epoxide hydrolase activity in human epidermal cells. Our results suggest that epidermal cells could cooperate in leukotriene B4 biosynthesis by transcellular metabolism of leukotriene A4 in lesions of psoriasis, and possibly other inflammatory dermatoses characterized by increased leukotriene B4 levels and prominent polymorphonuclear leukocyte infiltrates.