Carbon monoxide induces cytoprotection in rat orthotopic lung transplantation via anti-inflammatory and anti-apoptotic effects. Academic Article uri icon

Overview

MeSH

  • Animals
  • Caspase 3
  • Caspases
  • Cells, Cultured
  • Fibroblasts
  • Gene Expression Profiling
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Humans
  • In Situ Nick-End Labeling
  • Interleukin-6
  • Lung
  • Male
  • Membrane Proteins
  • Oligonucleotide Array Sequence Analysis
  • Peroxidase
  • Rats

MeSH Major

  • Anti-Inflammatory Agents
  • Apoptosis
  • Carbon Monoxide
  • Cytoprotection
  • Graft Rejection
  • Lung Transplantation

abstract

  • Successful lung transplantation has been limited by the high incidence of acute graft rejection. There is mounting evidence that the stress response gene heme oxygenase-1 (HO-1) and/or its catalytic by-product carbon monoxide (CO) confers cytoprotection against tissue and cellular injury. This led us to hypothesize that CO may protect against lung transplant rejection via its anti-inflammatory and antiapoptotic effects. Orthotopic left lung transplantation was performed in Lewis rat recipients from Brown-Norway rat donors. HO-1 mRNA and protein expression were markedly induced in transplanted rat lungs compared to sham-operated control lungs. Transplanted lungs developed severe intraalveolar hemorrhage, marked infiltration of inflammatory cells, and intravascular coagulation. However, in the presence of CO exposure (500 ppm), the gross anatomy and histology of transplanted lungs showed marked preservation. Furthermore, transplanted lungs displayed increased apoptotic cell death compared with the transplanted lungs of CO-exposed recipients, as assessed by TUNEL and caspase-3 immunostaining. CO exposure inhibited the induction of IL-6 mRNA and protein expression in lung and serum, respectively. Gene array analysis revealed that CO also down-regulated other proinflammatory genes, including MIP-1alpha and MIF, and growth factors such as platelet-derived growth factor, which were up-regulated by transplantation. These data suggest that the anti-inflammatory and antiapoptotic properties of CO confer potent cytoprotection in a rat model of lung transplantation.

publication date

  • July 2003

has subject area

  • Animals
  • Anti-Inflammatory Agents
  • Apoptosis
  • Carbon Monoxide
  • Caspase 3
  • Caspases
  • Cells, Cultured
  • Cytoprotection
  • Fibroblasts
  • Gene Expression Profiling
  • Graft Rejection
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Humans
  • In Situ Nick-End Labeling
  • Interleukin-6
  • Lung
  • Lung Transplantation
  • Male
  • Membrane Proteins
  • Oligonucleotide Array Sequence Analysis
  • Peroxidase
  • Rats

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1868152

Digital Object Identifier (DOI)

  • 10.1016/S0002-9440(10)63646-2

PubMed ID

  • 12819027

Additional Document Info

start page

  • 231

end page

  • 242

volume

  • 163

number

  • 1