Lipoxin Formation during Neutrophil-Platelet Interactions: a Role for Leukotriene A₄ and Platelet 12-Lipoxygenase

Abstract

The lipoxins are a series of biologically active eicosanoids which contain a conjugated tetraene structure as a characteristic feature (1). The two main compounds which carry biological activities are positional isomers: one designated lipoxin A₄ (5S,6R,15S-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acid) and the other lipoxin B₄ (5S,14R,15S, trihydroxy-6,10,12-trans-8-cis-eicosatetraenoic acid). Multiple pathways have been documented in vitro which can lead to the formation of lipoxins (1–4). It appears that the biosynthetic pathways utilized are species-, cell type- and substratespecific. One route, documented with results from both isotopic oxygen studies as well as the identification of alcohol trapping products, involves the transformation of 15-HETE to a 5(6)epoxytetraene by leukocytes (1). When this intermediate (15S-hydroxy-5,6-epoxy-7,9,13-trans-11-ciseicosatetraenoic acid) was synthesized and incubated with purified cytosolic epoxide hydrolase, it was quantitatively converted into LXA₄ (5). During the formation of lipoxins from exogenous 15-HETE by human neutrophils (an event which may occur in cell-cell interactions), an inverse relationship is observed between leukotriene and lipoxin production (6). Thus, the generation of epoxide-containing intermediates by human PMN appears to play a pivotal role in the biosynthesis of both leukotrienes and lipoxins.