Human platelets dose-dependently converted exogenous leukotriene A4 to leukotriene C4 and efficiently metabolized this compound to leukotrienes D4 and E4. Neither of these compounds were produced after stimulation of human platelet suspensions with ionophore A231 87. After LTA, incubation of subcellular fractions, formation of leukotriene C, was exclusively observed in the particulate fraction and was separable from the classical glutathione S-transferase activity. This suggested the presence of a specific leukotriene C4 synthase in human platelets. Addition of physiological amounts of autologous platelets to human granulocyte suspensions significantly increased ionophore A231 87-induced formation of leukotriene C4. In contrast, the production of leukotriene B4 was decreased. After preincubation of platelets with [35S]cysteine, 35S-labeled leukotriene C4 was produced by A231 87-stimulated platelet-granulocyte suspensions, strongly indicating a transcellular biosynthesis of this compound.The unstable epoxide, leukotriene A4 (LTA,), is formed by enzymatic transformation of arachidonic acid via two successive reactions catalysed by 5-lipoxygenase [l]. Conjugation of this compound with glutathione (GSH), leading to LTC4 formation, is catalysed by a specific particulate LTC4 synthase [2, 31 or various unspecific, mainly cytosolic GSH S-transferases [4, 51. Degradation of LTC4 is initiated by removal of a ;j-glutamyl group by y-glutamyl transpeptidase, leading to formation of LTD4. After subsequent elimination of glycine by a dipeptidase, LTE4 is formed [l]. Alternatively, LTA4 is stereospecifically converted by an LTA4 hydrolase to the potent leukocyte activator LTB4, or spontaneously hydrolysed to the biologically inactive stereoisomers, 6-trans-LTB4 and 1 2-epi,6-truns-LT B4 [6].Production of LTC4 has been reported in various leukocytes, including eosinophils, basophils, monocytes/ macrophages and mast cells [7]. Neutrophil granulocytes produce substantial amounts of LTB4, while LTC, is releascd in minute quantities [7, 81. In addition, neutrophils release LTA4 [9], which is available for further transformation by surrounding cells of various origin. Thus, erythrocytes [lo] and mast cells [9] converted neutrophil-derived LTA4 to LTB4 and LTC4, respectively. Furthermore, porcine endothelial and smooth muscle cells transformed LTA4, originating from polymorphonuclear granulocytes, to LTC4 [ll, 121, while human endothelial cells converted granulocyte-derived LTA4 to leukotrienes B4, C4, D4 and E4 [13].The cysteinyl-containing leukotrienes C,, D4 and E4 are potent mediators of smooth muscle contraction, increase microvascular permeability in the airways and stimulate mucus secretion [l]. Therefore, these compounds have been postulated to play an important role in bronchial asthma [I]. Involvement of platelets in the pathophysiology of asthma has been indicated [14]. In this respect, a recent report suggesting Correspondence to C. Edenius, lnslilulionen for Medicinsk Kemi 11, Karolinska Institutet, Box 60400, S-10401...