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) (LTB(4)) 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 (LTB(4) receptor), has recently been identified as an LTB(4) receptor. To determine if BLTR is the sole receptor mediating LTB(4)-induced leukocyte activation and to determine the role of LTB(4) 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 LTB(4)-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, LTB(4) 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 LTB(4)-induced leukocyte activation and establishes a model to decipher the functional roles of BLTR and LTB(4) in vivo.
Tager
A M
AM
Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Dufour
J H
JH
Goodarzi
K
K
Bercury
S D
SD
von Andrian
U H
UH
Luster
A D
AD
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion; D002630:Chemotactic Factors / Q000276:immunology*; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology* / Q000502:physiology; D018390:Gene Targeting; D007975:Leukotriene B4 / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009132:Muscles / Q000098:blood supply; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D010538:Peritonitis / Q000139:chemically induced / Q000276:immunology*; D018102:Receptors, Leukotriene B4 / Q000235:genetics / Q000276:immunology*; D013864:Thioglycolates / Q000276:immunology / Q000494:pharmacology; D014699:Venules
D002630:Chemotactic Factors; D018102:Receptors, Leukotriene B4; D013864:Thioglycolates; D007975:Leukotriene B4; D002118:Calcium