IngentaConnect A functional analysis of a natural variant of intercellular adhes...

Authors: Craig, Alister; Fernandez-Reyes, Delmiro; Mesri, Mehdi¹; McDowall, Alison²; Altieri, Dario C.¹; Hogg, Nancy²; Newbold, Christopher

Source: Human Molecular Genetics, Volume 9, Number 4, 1 March 2000 , pp. 525-530(6)

Publisher: Oxford University Press

Abstract:

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-1^Kilifi has reduced avidity for LFA-1 compared with ICAM-1^ref and binding to soluble fibrinogen was completely abolished with the Kilifi variant. In Plasmodium falciparum adhesion assays, ITO4-A4u binding to ICAM-1^Kilifi 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.

Document Type: Research article

Affiliations: 1: Boyer Center for Molecular Medicine, Yale University School of Medicine, 295 Congress Avenue, PO Box 9812, New Haven, CT 06536-0812, USA and 2: Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund Laboratories, PO Box123, Lincoln’s Inn Fields, London WC2A 3PX, UK

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

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