Calcium mobilization, actin polymerization and right-angle light scatter responses to leukotriene B4, 12(R)- and 12(S)-hydroxyeicosatetraenoic acid in human neutrophils

The presence of microgram quantities of 12(R)-hydroxyeicosatetraenoic acid (12(R)HETE) in psoriatic scales has been reported. 12(R)HETE has been found to be 5-10 times more potent than its isomer 12(S)HETE in inducing neutrophil locomotion and aggregation. In this study, the ability of these two eicosanoids to elicit a mobilization of calcium and a polymerization of actin was examined and compared to that of leukotriene B4. These two cell-biochemical assays were chosen in view of the likelihood that they are relevant to the motile functions of the neutrophils. 12(R)HETE was found to induce an increase in the cytoplasmic level of free calcium and in the amount of polymerized actin. 12(S)HETE also raised the level of free calcium, though to a lesser extent than 12(R)HETE, but did not induce a detectable polymerization of actin. Leukotriene B4 was more active, on the basis of concentration and maximal response, than either 12(R)HETE or 12(S)HETE. The activity of 12(R)HETE detected and reported in this communication provides support for the suggestion that this eicosanoid may play a significant role in the pathogenesis of the inflammatory reactions in psoriasis.