Plasmodium falciparum-infected erythrocytes bind ICAM-1 at a site distinct from LFA-1, Mac-1, and human rhinovirus.
The attachment of erythrocytes infected with P. falciparum to human venular endothelium is the primary step leading to complications from severe and cerebral malaria. Intercellular adhesion molecule-1 (ICAM-1, CD54) has been implicated as a cytoadhesion receptor for P. falciparum-infected erythrocytes. Characterization of domain deletion, human/murine chimeric ICAM-1 molecules, and amino acid substitution mutants localized the primary binding site for parasitized erythrocytes to the first amino-terminal immunoglobulin-like domain of ICAM-1. The ICAM-1 binding site is distinct from those recognized by LFA-1, Mac-1, and the human major-type rhinoviruses. Synthetic peptides encompassing the binding site on ICAM-1 inhibited malaria-infected erythrocyte adhesion to ICAM-1-coated surfaces with a Ki of 0.1-0.3 mM, whereas the Ki for soluble ICAM-1 is 0.15 microM. These findings have implications for the therapeutic reversal of malaria-infected erythrocyte sequestration in the host microvasculature.
Institute of Research, Walter Reed Army Medical Center, Washington, D.C. 20307.
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Ockenhouse
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Betageri
T A
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Springer
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DE
Staunton
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004912:Erythrocytes / Q000469:parasitology / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology*; D016177:Macrophage-1 Antigen / Q000502:physiology*; D016778:Malaria, Falciparum / Q000097:blood*; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010963:Plasmodium falciparum / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology*; D012229:Rhinovirus / Q000502:physiology*; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D011991:Receptors, Virus; D018799:Intercellular Adhesion Molecule-1