A functional analysis of a natural variant of intercellular adhesion molecule-1 (ICAM-1Kilifi).
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 wit...
| Glavni autori: | , , , , , , |
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| Format: | Journal article |
| Jezik: | English |
| Izdano: |
2000
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| _version_ | 1826269826440495104 |
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| author | Craig, A Fernandez-Reyes, D Mesri, M McDowall, A Altieri, D Hogg, N Newbold, C |
| author_facet | Craig, A Fernandez-Reyes, D Mesri, M McDowall, A Altieri, D Hogg, N Newbold, C |
| author_sort | Craig, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T21:31:14Z |
| format | Journal article |
| id | oxford-uuid:44bef8c7-1c8f-41b3-8637-4129a91b9906 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:31:14Z |
| publishDate | 2000 |
| record_format | dspace |
| spelling | oxford-uuid:44bef8c7-1c8f-41b3-8637-4129a91b99062022-03-26T15:03:32ZA functional analysis of a natural variant of intercellular adhesion molecule-1 (ICAM-1Kilifi).Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:44bef8c7-1c8f-41b3-8637-4129a91b9906EnglishSymplectic Elements at Oxford2000Craig, AFernandez-Reyes, DMesri, MMcDowall, AAltieri, DHogg, NNewbold, CIntercellular 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. |
| spellingShingle | Craig, A Fernandez-Reyes, D Mesri, M McDowall, A Altieri, D Hogg, N Newbold, C A functional analysis of a natural variant of intercellular adhesion molecule-1 (ICAM-1Kilifi). |
| title | A functional analysis of a natural variant of intercellular adhesion molecule-1 (ICAM-1Kilifi). |
| title_full | A functional analysis of a natural variant of intercellular adhesion molecule-1 (ICAM-1Kilifi). |
| title_fullStr | A functional analysis of a natural variant of intercellular adhesion molecule-1 (ICAM-1Kilifi). |
| title_full_unstemmed | A functional analysis of a natural variant of intercellular adhesion molecule-1 (ICAM-1Kilifi). |
| title_short | A functional analysis of a natural variant of intercellular adhesion molecule-1 (ICAM-1Kilifi). |
| title_sort | functional analysis of a natural variant of intercellular adhesion molecule 1 icam 1kilifi |
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