Holder, A L and Wolf, S and Walshe, C and Pandya, P and Stanford, R E and Smith, J D and Rose, M L and Lawson, C (2008) 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). pp. 71-78.
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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.
Item Type: | Article |
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RVC Publication Type: | Research (full) paper |
WoS ID: | 000254790000001 |
DOI: | https://doi.org/10.1016/j.humimm.2007.12.004 |
Departments: | Comparative Biomedical Sciences |
Depositing User: | RVC Auto-import |
Last Modified: | 21 Nov 2020 15:43 |
URI: | https://researchonline.rvc.ac.uk/id/eprint/1497 |
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