Identification of a Plasmodium falciparum intercellular adhesion molecule-1 binding domain: a parasite adhesion trait implicated in cerebral malaria.
In: Proceedings of the National Academy of Sciences of the United States of America, Jg. 97 (2000-02-15), Heft 4, S. 1766-71
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Zugriff:
Binding of infected erythrocytes to brain venules is a central pathogenic event in the lethal malaria disease complication, cerebral malaria. The only parasite adhesion trait linked to cerebral sequestration is binding to intercellular adhesion molecule-1 (ICAM-1). In this report, we show that Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) binds ICAM-1. We have cloned and expressed PfEMP1 recombinant proteins from the A4tres parasite. Using heterologous expression in mammalian cells, the minimal ICAM-1 binding domain was a complex domain consisting of the second Duffy binding-like (DBL) domain and the C2 domain. Constructs that contained either domain alone did not bind ICAM-1. Based on phylogenetic criteria, there are five distinct PfEMP1 DBL types designated alpha, beta, gamma, delta, and epsilon. The DBL domain from the A4tres that binds ICAM-1 is DBLbeta type. A PfEMP1 cloned from a distinct ICAM-1 binding variant, the A4 parasite, contains a DBLbeta domain and a C2 domain in tandem arrangement similar to the A4tres PfEMP1. Anti-PfEMP1 antisera implicate the DBLbeta domain from A4var PfEMP1 in ICAM-1 adhesion. The identification of a P. falciparum ICAM-1 binding domain may clarify mechanisms responsible for the pathogenesis of cerebral malaria and lead to interventions or vaccines that reduce malarial disease.
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Identification of a Plasmodium falciparum intercellular adhesion molecule-1 binding domain: a parasite adhesion trait implicated in cerebral malaria.
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Autor/in / Beteiligte Person: | Smith, JD ; Craig, AG ; Kriek, N ; Hudson-Taylor, D ; Kyes, S ; Fagan, T ; Pinches, R ; Baruch, DI ; Newbold, CI ; Miller, LH |
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Zeitschrift: | Proceedings of the National Academy of Sciences of the United States of America, Jg. 97 (2000-02-15), Heft 4, S. 1766-71 |
Veröffentlichung: | Washington, DC : National Academy of Sciences, 2000 |
Medientyp: | academicJournal |
ISSN: | 0027-8424 (print) |
DOI: | 10.1073/pnas.040545897 |
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