Mechanisms for Diversification of Responses of Human Polymorphonuclear Leukocytes to Leukotrienes

Abstract

The oxidative metabolism of arachidonic acid proceeds by complex pathways resulting in the generation of an array of structurally distinct and biologically potent mediators of physiological, as well as pathological events (Samuelsson, 1983; Goetzl & Scott, 1984). The leukotrienes (LTs) are products of the 5-lipoxygenase pathway found in mast cells, polymorphonuclear (PMN) leukocytes and macrophages (Samuelsson, 1983), and exhibit two classes of activities (Goetzl, 1980). The sulfidopeptide LTs (LTC₄, LTD₄, LTE₄) are smooth muscle contractile and vasoactive factors, that account for the activities of slow-reacting substance of anaphylaxis or SRS-A (Goetzl et al., 1983; Hedqvist et al., 1985; Piper & Samboun, 1982; Krell et al., 1985). In addition, the sulfidopeptide LTs stimulate glandular and epithelial cell secretion and alter some proliferative and transport processes (Samuelsson, 1983; Goetzl, 1980; Lewis & Austen, 1984; Dahlen et al., 1980; Pologe et al., 1984; Johnson & Torres, 1984; Pek & Walsh, 1984). The specific di-hydroxy-LT or LTB₄, on the other hand, elicits PMN leukocyte and eosinophil chemotaxis, initiates PMN leukocyte lysosomal enzyme secretion, and stimulates the respiratory burst (Goetzl & Pickett, 1981; Nagy et al., 1982; Bray et al., 1981). In addition, LTB₄ also inhibits proliferative responses of mixed T-lymphocytes to mitogen and antigens, by separate and opposing effects on the helper and suppressor subsets of T-cells (Payan & Goetzl, 1983; Payan et al., 1984; Gaulde et al., 1985).