The polymorphonuclear leukocyte: A cell tuned for transcellular biosynthesis of cys-leukotrienes

Sulfidopeptide leukotrienes (cysLT) are potent vasoactive mediators that can constrict coronary vessels and alter caliber of the microcirculation. They can be formed "in situ" via in a peculiar type of cell communication termed "transcellular biosynthesis" whereby donor cells (polymorphonuclear leukocytes, PMNL) feed acceptor cells (endothelial cells, EC) the unstable epoxide intermediate leukotriene A(4) for further metabolism to cysLT. We have investigated the relative amount of leukotriene A(4) that is synthesized by PMNL and made available for transcellular biosynthesis. This has been accomplished by measuring the relative amounts of enzymatic vs non-enzymatic leukotriene A(4)-derived metabolites after challenge with the Ca2+-ionophore A23187, using PMNL suspensions at different concentrations. Non-enzymatic leukotriene A(4)-derived metabolites were used as a quantitative index of the amount of leukotriene A(4) released into the extracellular milieu. In human, as well as in bovine PMNL, the relative amounts of non-enzymatic vs enzymatic leukotriene A(4)-derived metabolites increased with decreasing cells concentrations. By diminishing possible cell-cell interactions via increased dilution, it is calculated that approx. 60% of leukotriene A(4) synthesized is released from the PMNL. These data provide evidence that, in PMNL, transfer of leukotriene A(4) to neighbouring acceptor cells is taking place as a predominant mechanism of cell communication.