Expression of endothelial intercellular adhesion molecule-1 is determined by genotype: Effects on efficiency of leukocyte adhesion to human endothelial cells

Holder, A L; Wolf, S; Walshe, C; Pandya, P; Stanford, R E; Smith, J D; Rose, M L; Lawson, C

Abstract

Two bialletic polymorphisms, previously described in the human intercellular adhesion molecule (ICAM)-1 gene at codon 241 (glycine [G] to arginine [R] substitution) and codon 469 (glutamic acid [E] to lysine [K] substitution) have been associated with a number of diseases including myocardial infarction, transplant rejection, and diabetes. However, the functional significance of these polymorphisms has not been determined. ICAM-1 cell surface expression and ICAM-1-mediated Leukocyte adhesion were investigated using Cos7 transfected with ICAM-1 polymorphic variants or human umbilical vein endothelial cells (HUVEC) of different ICAM-1 genotypes. There was significantly higher expression of surface ICAM-1 on Cos7 transfected with a plasmid encoding the GE (G241/E469) ICAM-1 variant or untreated HUVEC of GEGE (G241/E469 homozygous genotype). ICAM-1-mediated adhesion of peripheral blood mononuclear cells (PBMC) to GE-Cos7 cells or TNF-treated GEGE HUVEC was significantly increased. However, there was no significant difference in adhesion of PBMC to recombinant ICAM-1 of each polymorphic variant plated onto plastic wells. We conclude that the GE genotype of ICAM-1 is associated with greater cell surface expression of ICAM-1, which in turn leads to greater adhesion of leukocytes. This may explain the previously described associations of ICAM-1 polymorphisms with chronic inflammatory disease. (C) 2008 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Citation

Holder, A. L., Wolf, S., Walshe, C., Pandya, P., Stanford, R. E., Smith, J. D., …Lawson, C. Expression of endothelial intercellular adhesion molecule-1 is determined by genotype: Effects on efficiency of leukocyte adhesion to human endothelial cells. Human Immunology, 69(2), 71-78. https://doi.org/10.1016/j.humimm.2007.12.004

• Journal Article Type: Article
• Deposit Date: Nov 12, 2014
• Journal: Human Immunology
• Print ISSN: 0198-8859
• Publisher: Elsevier
• Volume: 69
• Issue: 2
• Pages: 71-78
• DOI: https://doi.org/10.1016/j.humimm.2007.12.004
• Public URL: https://rvc-repository.worktribe.com/output/1429670
• Additional Information: Corporate Creators : Imperial College London