A functional analysis of a natural variant of intercellular adhesion molecule-1 (ICAM-1Kilifi).

Journal article

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.

Authors: Craig, A; Fernandez-Reyes, D; Mesri, M; McDowall, A; Altieri, D

• Journal: Human molecular genetics
• Volume: 9
• Issue: 4
• Pages: 525-530
• Publication date: 2000-03-01
• DOI: 10.1093/hmg/9.4.525
• EISSN: 1460-2083
• ISSN: 0964-6906
• Language: English
• Keywords: Protein Binding; Cell Adhesion; Cells, Cultured; Recombinant Fusion Proteins; Lymphocyte Function-Associated Antigen-1; T-Lymphocytes; Kenya; Plasmodium falciparum; Humans; Malaria, Cerebral; Intercellular Adhesion Molecule-1; Immunoglobulin Fc Fragments; Fibrinogen; Genetic Variation; Mutagenesis, Site-Directed; Animals