Cardiac Allograft Survival in Mice Deficient in Intercellular Adhesion Molecule–1 Article (Web of Science)

abstract

  • Background Intercellular adhesion molecule–1 (ICAM-1, CD54) is a cell adhesion molecule that interacts with the leukocyte β2 integrins, lymphocyte function–associated antigen–1, and macrophage antigen–1. ICAM-1 is postulated to play a key role in several cell-cell interactions that are important in allograft rejection, including antigen presentation, transendothelial migration of leukocytes, and leukocyte-mediated myocyte injury. Methods and Results Mice homozygous for a gene-targeted mutation of ICAM-1 were used in two different cardiac transplant models to further define the role of ICAM-1 in the process of allograft rejection. In the first model, hearts from newborn mice were implanted in the ear pinnae of H -2–incompatible recipients. In the second model, intra-abdominal transplantation by direct vascular anastomosis was performed. Time to rejection was defined by the loss of pulsatile activity assessed by visual inspection in the ear model or by cessation of palpable cardiac impulse in the abdominal model. Allograft survival did not differ significantly between control groups that express normal levels of ICAM-1 and those groups using ICAM-1–deficient mutants as either donors or recipients. Histological examination of rejection of both normal and mutant (ICAM-1-deficient) cardiac allografts revealed similar patterns of infiltration of mononuclear and granulocytic leukocytes and myocyte necrosis. Immunostaining with anti–ICAM-1 antibodies showed ICAM-1–positive infiltrating cells in both mutant (ICAM-1–deficient) and normal allografts, with the graft endothelium negative for ICAM-1 staining in the mutant allografts. Conclusions The absence of surface expression of ICAM-1 in the donor allograft or recipient is insufficient to produce a significant impact on cardiac allograft survival. This study highlights the need to understand more precisely the mechanism of action whereby monoclonal antibodies to ICAM-1 prolong cardiac allograft survival before new therapeutic strategies based on gene transfer technology or small molecule inhibitors are developed. Mutant mice with targeted mutations in cell adhesion molecules provide powerful tools to study the complex role that cell adhesion molecules play in the cellular interactions between donor graft tissue and the recipient that culminate in graft rejection.

authors

  • Schowengerdt, Kenneth O.
  • Zhu, Jessica Y.
  • Stepkowski, Stanislaw M
  • Tu, Yizheng
  • Entman, Mark L.
  • Ballantyne, Christie M.

publication date

  • 1995

webpage

published in

number of pages

  • 5

start page

  • 82

end page

  • 87

volume

  • 92

issue

  • 1