Bltr Mediates Leukotriene B₄–Induced Chemotaxis and Adhesion and Plays a Dominant Role in Eosinophil Accumulation in a Murine Model of Peritonitis

Leukotriene B₄ (LTB₄) is a potent chemoattractant active on multiple leukocytes, including neutrophils, macrophages, and eosinophils, and is implicated in the pathogenesis of a variety of inflammatory processes. A seven transmembrane–spanning, G protein–coupled receptor, called BLTR (LTB₄ receptor), has recently been identified as an LTB₄ receptor. To determine if BLTR is the sole receptor mediating LTB₄-induced leukocyte activation and to determine the role of LTB₄ and BLTR in regulating leukocyte function in inflammation in vivo, we generated a BLTR-deficient mouse by targeted gene disruption. This mouse reveals that BLTR alone is responsible for LTB₄-mediated leukocyte calcium flux, chemotaxis, and firm adhesion to endothelium in vivo. Furthermore, despite the apparent functional redundancy with other chemoattractant–receptor pairs in vitro, LTB₄ and BLTR play an important role in the recruitment and/or retention of leukocytes, particularly eosinophils, to the inflamed peritoneum in vivo. These studies demonstrate that BLTR is the key receptor that mediates LTB₄-induced leukocyte activation and establishes a model to decipher the functional roles of BLTR and LTB₄ in vivo.