Polymorphonuclear-Endothelial Cell Interactions and the Control of Coronary Vasculature

Abstract

The generation of leukotrienes (LTs) exhibits remarkable cellular specificity; both PMNL and eosinophils contain the 5-lipoxygenase (5-LO) enzyme, a single protein possessing both the dioxygenase activity necessary for the synthesis of 5-hydroperoxy eicosatetraenoic acid (5-HPETE), and the epoxygenase activity leading to leukotriene A4 (LTA4)(Shimizu et al, 1984). This unstable allylic epoxide can be further converted by secondary enzymes, i.e. LTA4 hydrolase and leukotriene C4 (LTC4) synthase, into leukotriene B4 (LTB4) or LTC4 respectively (Lewis & Austen, 1984). Following challenge with the calcium ionophore A23187 (Borgeat & Samuelsson, 1979), PMNL generate predominantly LTB4, a compound with very potent chemoattractant activities. On the other hand eosinophils (Weller et al., 1983) show preferential generation of LTC4, a potent bronchoconstrictor. Recently it has been shown that the two biosynthetic steps leading to bioactive leukotrienes, can be carried out by different cell types, whereby PMNL (i.e. donor cells) can synthesize the unstable metabolic intermediate LTA4 which can be metabolized by vicinal cells (i.e. acceptor cells) into LTs B4 or C4. Such reaction involves the cooperation of PMNL with erythrocytes, platelets, endothelial cell (McGee & Fitzpatrick, 1986; Maclouf & Murphy, 1988; Feinmark & Cannon, 1986 and 1987; Marcus et al., 1982). This process has been termed “transcellular biosynthesis” and suggests that the cellular environment (i.e. cell-cell interaction) is an important control in the production of eicosanoids (Maclouf et al., 1989). Most in vitro studies of transcellular biosynthesis have used cells isolated from blood or cultured endothelial cells as a reflection of what might happen in pathological situations such as in inflammatory reactions or in cardiovascular diseases where cell-cell interactions constitute an important part of this process (Lucchesi & Mullane, 1986).