Molecular cloning and characterization of leukotriene B4 receptor.

Abstract

Leukotriene B4 (LTB4) is a potent proinflammatory and chemotactic factor biosynthesized in various tissues, which is involved in inflammation, immune responses and host defense against infection.1 LTB4 activates inflammatory cells by binding to its cell-surface receptor (BLT). Specific binding for [3H]LTB4 was reported in the membrane fractions of granulocytes, T lymphocytes, alveolar macrophages, spleen, brain, THP-1 cells, and differentiated HL-60 cells.2–5 By addition of GTPγS, low affinity sites of [3H]LTB4 binding appeared in spleen membranes.5 LTB4 stimulated a dose-dependent increase in GTP hydrolysis in HL-60 cells.6 LTB4 induced increase in intracellular calcium, D-myo-inositol-l,4,5-triphosphate (InsP3) accumulation, O2-production, and activation of GTPase in a pertussis toxin (PTX)-sensitive manner.7,8 On the other hand, LTB4-induced hyperadhesiveness of vascular endothelial cells was reported to be PTX-insensitive.9 These data indicated the presence of BLT coupled with G-protein(s). However, BLT had not been purified to homogeneity or cDNA-cloned.