Leukotriene B4 and BLT1 control cytotoxic effector T cell recruitment to inflamed tissues.
Leukotriene B4 (LTB4) is a potent chemoattractant for myeloid leukocytes, which express BLT1, the high-affinity receptor for LTB4. We report here that BLT1 is induced substantially in CD8+ effector T cells and at lower amounts in CD8+ central memory T cells. LTB4 elicited BLT1-dependent chemotaxis in effector cells, but not in naive or central memory cells. Intravital microscopy showed that BLT1 signaling induced rapid integrin-mediated arrest of rolling effector and central memory cells in postcapillary venules. In competitive homing experiments, wild-type effector cells were three times more efficient at migrating to the inflamed peritoneal cavity than were BLT-deficient effector cells. These results identify LTB4-BLT1 as a potent nonchemokine pathway for cytotoxic effector cell traffic.
Goodarzi
Katayoon
K
Center for Blood Research and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Goodarzi
Mahmoud
M
Tager
Andrew M
AM
Luster
Andrew D
AD
von Andrian
Ulrich H
UH
D000208:Acute Disease; D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000276:immunology; D016023:Integrins / Q000276:immunology; D007975:Leukotriene B4 / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000098:blood supply / Q000276:immunology; D010538:Peritonitis / Q000276:immunology; D018102:Receptors, Leukotriene B4 / Q000096:biosynthesis / Q000276:immunology*; D016201:Receptors, Lymphocyte Homing / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D016023:Integrins; D018102:Receptors, Leukotriene B4; D016201:Receptors, Lymphocyte Homing; D007975:Leukotriene B4