Ischemia-reperfusion injury activates innate immunity in rat kidneys

Transplantation. 2005 May 27;79(10):1370-7. doi: 10.1097/01.tp.0000158355.83327.62.

Abstract

Background: There is growing evidence of a role of the immune system in the pathophysiology of ischemia-reperfusion (I/R) injury, but the influence of I/R injury on innate immunity is still undetermined.

Methods: Sprague-Dawley rats were used. I/R injury was induced by clamping both renal arteries for 45 min, and the rats were killed 1, 3, 5, and 7 days later. Activation of innate immunity was evaluated in terms of the expression of toll-like receptor (TLR) 2 or TLR4 mRNAs and protein, by the level of the TLR ligand (heat shock protein [HSP] 70), and maturation of dendritic cells by double-label immunohistochemistry of dendritic cells for major histocompatibility complex (MHC) class II antigen.

Results: I/R injury increased TLR2 and TLR4 mRNA and protein expression, and they were mainly observed on renal tubular cells. I/R injury also produced endogenous TLR ligand (HSP70) on renal tubular cells. I/R injury increased not only the numbers of dendritic cells but also the production of MHC class II antigen in dendritic cells, suggesting maturation of these cells. Activation of innate immunity was observed at day 1, peaked at days 3 to 5 after I/R injury, and thereafter gradually decreased.

Conclusions: I/R injury rapidly activates the innate immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Formation
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • HSP70 Heat-Shock Proteins / metabolism
  • Histocompatibility Antigens Class II / biosynthesis
  • Histocompatibility Antigens Class II / metabolism
  • Immunity, Innate*
  • Kidney / immunology*
  • Kidney / pathology
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Reperfusion Injury / immunology*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors

Substances

  • HSP70 Heat-Shock Proteins
  • Histocompatibility Antigens Class II
  • Membrane Glycoproteins
  • RNA, Messenger
  • Receptors, Cell Surface
  • Tlr2 protein, rat
  • Tlr4 protein, rat
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors