Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants. Academic Article uri icon

Overview

MeSH

  • Acute Disease
  • Animals
  • Apoptosis
  • Cell Line
  • Cell Movement
  • Endothelium, Vascular
  • Environmental Exposure
  • Enzyme Activation
  • Graft Survival
  • Heme Oxygenase-1
  • Macrophages
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Monocytes
  • Muscle, Smooth, Vascular
  • Platelet Aggregation
  • Rats
  • Rats, Inbred Lew
  • Thrombosis
  • Up-Regulation

MeSH Major

  • Carbon Monoxide
  • Graft Rejection
  • Heart Transplantation
  • Heme Oxygenase (Decyclizing)
  • Transplantation, Heterologous

abstract

  • Mouse-to-rat cardiac transplants survive long term after transient complement depletion by cobra venom factor and T cell immunosuppression by cyclosporin A. Expression of heme oxygenase-1 (HO-1) by the graft vasculature is critical to achieve graft survival. In the present study, we asked whether this protective effect was attributable to the generation of one of the catabolic products of HO-1, carbon monoxide (CO). Our present data suggests that this is the case. Under the same immunosuppressive regimen that allows mouse-to-rat cardiac transplants to survive long term (i.e., cobra venom factor plus cyclosporin A), inhibition of HO-1 activity by tin protoporphyrin, caused graft rejection in 3--7 days. Rejection was associated with widespread platelet sequestration, thrombosis of coronary arterioles, myocardial infarction, and apoptosis of endothelial cells as well as cardiac myocytes. Under inhibition of HO-1 activity by tin protoporphyrin, exogenous CO suppressed graft rejection and restored long-term graft survival. This effect of CO was associated with inhibition of platelet aggregation, thrombosis, myocardial infarction, and apoptosis. We also found that expression of HO-1 by endothelial cells in vitro inhibits platelet aggregation and protects endothelial cells from apoptosis. Both these actions of HO-1 are mediated through the generation of CO. These data suggests that HO-1 suppresses the rejection of mouse-to-rat cardiac transplants through a mechanism that involves the generation of CO. Presumably CO suppresses graft rejection by inhibiting platelet aggregation that facilitates vascular thrombosis and myocardial infarction. Additional mechanisms by which CO overcomes graft rejection may involve its ability to suppress endothelial cell apoptosis.

publication date

  • March 15, 2001

has subject area

  • Acute Disease
  • Animals
  • Apoptosis
  • Carbon Monoxide
  • Cell Line
  • Cell Movement
  • Endothelium, Vascular
  • Environmental Exposure
  • Enzyme Activation
  • Graft Rejection
  • Graft Survival
  • Heart Transplantation
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Macrophages
  • Male
  • Membrane Proteins
  • Mice
  • Mice, Inbred BALB C
  • Monocytes
  • Muscle, Smooth, Vascular
  • Platelet Aggregation
  • Rats
  • Rats, Inbred Lew
  • Thrombosis
  • Transplantation, Heterologous
  • Up-Regulation

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 11238670

Additional Document Info

start page

  • 4185

end page

  • 4194

volume

  • 166

number

  • 6