Leukotriene B4 and BLT1 control cytotoxic effector T cell recruitment to inflamed tissues

Nat Immunol. 2003 Oct;4(10):965-73. doi: 10.1038/ni972. Epub 2003 Aug 31.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Animals
  • Chemotaxis, Leukocyte / immunology
  • Flow Cytometry
  • Immunologic Memory / immunology
  • Integrins / immunology
  • Leukotriene B4 / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Skeletal / blood supply
  • Muscle, Skeletal / immunology
  • Peritonitis / immunology
  • Receptors, Leukotriene B4 / biosynthesis
  • Receptors, Leukotriene B4 / immunology*
  • Receptors, Lymphocyte Homing / immunology
  • Signal Transduction / immunology*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Integrins
  • Receptors, Leukotriene B4
  • Receptors, Lymphocyte Homing
  • Leukotriene B4