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Murine Cervical Heart Transplantation Model Using a Modified Cuff Technique
Published on: October 12, 2014
Cardiac allograft survival in mice deficient in intercellular adhesion molecule-1
K O Schowengerdt1, J Y Zhu, S M Stepkowski
1Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
Insights
Intercellular adhesion molecule-1 (ICAM-1) deficiency did not significantly impact cardiac allograft survival in mice. This suggests ICAM-1 alone is insufficient to prevent rejection, necessitating further research into its precise role in transplantation.
Area of Science:
- Immunology
- Transplantation Biology
- Molecular Medicine
Background:
- Intercellular adhesion molecule-1 (ICAM-1, CD54) is a cell adhesion molecule crucial for leukocyte interactions.
- ICAM-1 is implicated in allograft rejection processes like antigen presentation and leukocyte migration.
Purpose of the Study:
- To investigate the role of ICAM-1 in cardiac allograft rejection using gene-targeted mutant mice.
- To determine if ICAM-1 deficiency in donors or recipients affects allograft survival and rejection patterns.
Main Methods:
- Utilized two cardiac transplant models in mice: ear pinna and intra-abdominal.
- Employed ICAM-1-deficient mice as donors or recipients alongside wild-type controls.
- Assessed allograft survival by monitoring pulsatile activity or palpable impulse and performed histological analysis.
Main Results:
- Cardiac allograft survival did not significantly differ between ICAM-1-deficient and normal control groups.
- Histological examination revealed similar leukocyte infiltration and myocyte necrosis in both groups.
- Immunostaining showed ICAM-1-positive infiltrating cells in all grafts, with absent endothelial ICAM-1 in mutant allografts.
Conclusions:
- Absence of ICAM-1 on donor or recipient cells is insufficient to significantly alter cardiac allograft survival.
- Further research is needed to understand ICAM-1's mechanism in prolonging allograft survival for therapeutic development.
- Mutant mice are valuable tools for studying cell adhesion molecule roles in graft rejection.
Background:
Intercellular adhesion molecule-1 (ICAM-1, CD54) is a cell adhesion molecule that interacts with the leukocyte beta 2 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-medicated 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.
