IDENTIFICATION AND CHARACTERIZATION OF A HIGH-AFFINITY LEUKOTRIENE B-4 RECEPTOR ON GUINEA-PIG T-LYMPHOCYTES AND ITS REGULATION BY LIPOXIN A(4)

A single class of high affinity leukotriene B-4 (LTB(4)) receptors has been identified on the surface of guinea pig peritoneal exudate T lym phocytes. The K-d of these receptors is 1.6 nM, with a B-max of 25.2 f mol/10(7) cells (1500 sites/cell). Receptor binding activity can be bl ocked by specific LTB(4) receptor antagonists, but not by a specific L TD(4) receptor antagonist, lipoxins A(4) or B-4 (LXA(4), LXB(4)) or K2 52a, a protein kinase C inhibitor. Pretreatment of T lymphocytes with phorbol myristyl acetate or LXA(4), reduced LTB(4) receptor density in a concentration-dependent manner, although similar concentrations of LXB(4) had no effect. LTB(4) receptor down-modulation by LXA(4) was re versed by K252a. 4 alpha-Phorbol 12,18-didecanoate, an inactive struct ural analogue of phorbol myristyl acetate, did not activate protein ki nase C or decrease LTB(4) receptor density. These results suggest that LTB(4) receptor density on T cells may be ultimately down-regulated b y a protein kinase C-dependent mechanism and are consistent with a phy siological role of LXA(4) in the modulation of inflammatory process.