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Intercellular adhesion molecule-1 (ICAM-1) is involved in a range of interactions both within the host and between the host and a number of pathogens. Recently we described a mutation within the coding region of the first N-terminal immunoglobulin-like domain of ICAM-1, present at high frequency within African populations, which increased the risk of cerebral malaria. To understand the mechanism by which such a polymorphism might be maintained despite counter-selection by malaria, we have carried out functional assays using both forms of ICAM-1 as soluble Fc chimeric fusion proteins. ICAM-1Kilifi has reduced avidity for LFA-1 compared with ICAM-1ref and binding to soluble fibrinogen was completely abolished with the Kilifi variant. In Plasmodium falciparum adhesion assays, ITO4-A4u binding to ICAM-1Kilifi was reduced compared with binding to the reference form. These results allow for the possibility of balanced selection between the reference and Kilifi forms of ICAM-1 through modulation of inflammatory responses and indicate the existence of differences within ICAM-1-binding P. falciparum isolates which may be relevant to pathogenesis.

Original publication

DOI

10.1093/hmg/9.4.525

Type

Journal article

Journal

Hum Mol Genet

Publication Date

01/03/2000

Volume

9

Pages

525 - 530

Keywords

Animals, Cell Adhesion, Cells, Cultured, Fibrinogen, Genetic Variation, Humans, Immunoglobulin Fc Fragments, Intercellular Adhesion Molecule-1, Kenya, Lymphocyte Function-Associated Antigen-1, Malaria, Cerebral, Mutagenesis, Site-Directed, Plasmodium falciparum, Protein Binding, Recombinant Fusion Proteins, T-Lymphocytes