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BLTR mediates leukotriene B(4)-induced chemotaxis and adhesion and plays a dominant role in eosinophil accumulation in a murine model of peritonitis.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2000 Aug 07; Vol. 192 (3), pp. 439-46. - Publication Year :
- 2000
-
Abstract
- 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.
- Subjects :
- Animals
Calcium metabolism
Cell Adhesion
Disease Models, Animal
Eosinophils physiology
Gene Targeting
Macrophages, Peritoneal immunology
Macrophages, Peritoneal metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Muscles blood supply
Neutrophils immunology
Neutrophils metabolism
Peritonitis chemically induced
Receptors, Leukotriene B4 genetics
Thioglycolates immunology
Thioglycolates pharmacology
Venules
Chemotactic Factors immunology
Chemotaxis, Leukocyte
Eosinophils immunology
Leukotriene B4 immunology
Peritonitis immunology
Receptors, Leukotriene B4 immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1007
- Volume :
- 192
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 10934232
- Full Text :
- https://doi.org/10.1084/jem.192.3.439