Postischemic vascular permeability requires both TLR-2 and TLR-4, but only TLR-2 mediates the transendothelial migration of leukocytes

Shock. 2009 Jun;31(6):592-8. doi: 10.1097/SHK.0b013e318193c859.

Abstract

Ischemia-reperfusion (I/R) activates innate immunity involving Toll-like receptor (TLR) 2 and TLR-4 signaling. Leukocyte migration and vascular permeability contribute to postischemic tissue damage. We hypothesized that TLR-2 and TLR-4 directly mediate leukocyte migration and vascular permeability during I/R. We used in vivo microscopy on postischemic murine cremaster muscle to quantify leukocyte adhesion as well as transendothelial and interstitial migration in sham-operated wild-type mice and in wild-type, TLR-2(-/-), and TLR-4-mutant mice 30 and 120 min after I/R. Alterations in fluorescein isothiocyanate-dextran leakage across cremasteric venules were determined as a measure of endothelial permeability. I/R-induced leukocyte adhesion in TLR-2(-/-) and TLR-4-mutant mice was comparable to that in wild-type mice. The number of transmigrated leukocytes was increased upon I/R in wild-type mice as compared with the sham-operated group. In contrast, leukocyte transmigration was significantly attenuated in TLR-2(-/-) but not in TLR-4-mutant mice. Motility and polarization of interstitially migrating leukocytes did not significantly differ in TLR-2(-/-) and TLR-4-mutant mice from wild-type mice. Postischemic vascular leakage was significantly lower in both TLR-2(-/-) and TLR-4-mutant than in wild-type mice. We conclude that both TLR-2 signaling and TLR-4 signaling enhance postischemic vascular permeability and that TLR-2 has additional effects on the transendothelial migration of leukocytes at the postischemic vascular wall.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Capillary Permeability / genetics
  • Capillary Permeability / physiology*
  • Cell Adhesion / genetics
  • Cell Adhesion / physiology
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Leukocyte Count
  • Leukocytes / cytology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Microscopy, Fluorescence
  • Reperfusion Injury / physiopathology*
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / physiology*
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / physiology*

Substances

  • Toll-Like Receptor 2
  • Toll-Like Receptor 4