Printed:n U.S.A Identification and Characterization of a High-Affinity

A single class of high affinity leukotriene B4 (LTB4) receptors has been identified on the surface of guinea pig peritoneal exudate T lymphocytes. The Kd of these receptors is 1.6 nM, with a BmHE of 25.2 fmoVl O cells (1 500 sites/cell). Receptor binding activity can be blocked by specific LTB4 receptor an-tagonists, but not by a specific LTD4 receptor antagonist, Ii-poxins A4 or B4 (LXA, LXB4) or K252a, a protein kinase C inhibitor. Pretreatment of T lymphocytes with phorbol myristyl acetate or LXA4, reduced LTB4 receptor density in a concen-tration-dependent manner, although similar concentrations of LXB4 had no effect. LTB4 receptor down-modulation by LXA4 was reversed by K252a. 4a-Phorbol 12,13-didecanoate, an inactive structural analogue of phorbol myristyl acetate, did not activate protein kinase C or decrease LTB4 receptor density. These results suggest that LTB4 receptor density on T cells may be ultimately down-regulated by a protein kinase C-dependent mechanism and are consistent with a physiological role of LXA in the modulation of inflammatory process. LTB4 is a potent inflammatory mediator which partici-pates in various leukocyte activities, such as adhesion, chemotaxis, aggregation and degranulation (Samuelsson