BLTR mediates leukotriene B-4-induced chemotaxis and adhesion and plays a dominant role in eosinophil accumulation in a murine model of peritonitis

Leukotriene B-4 (LTB4) is a potent chemoattractant active on multiple leuko cytes. including neutrophils, macrophages, and eosinophils, and is implicat ed in the pathogenesis of a variety of inflammatory processes. A seven tran smembrane-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 deter mine the role of LTB4 and BLTR in regulating leukocyte function in inflamma tion in vivo, we generated a BLTR-deficient mouse by targeted gene disrupti on. This mouse reveals that BLTR alone is responsible for LTB4-mediated leu kocyte calcium flux, chemotaxis, and firm adhesion to endothelium in vivo. Furthermore, despite the apparent functional redundancy with other chemoatt ractant-receptor pairs in vitro, LTB4 and BLTR play an important role in th e 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 establish es a model to decipher the functional roles of BLTR and LTB4 in vivo.