A Receptor for the Malarial Parasite Plasmodium vivax : the Erythrocyte Chemokine Receptor

• DOI: 10.1126/science.7689250
• Publication Date: 2006-10-05T23:05:09Z
• Authors: Richard Horuk; Chetan E. Chitnis; Walter C. Darbonne; Timothy J. Colby; Anne Rybicki; Terence J. Hadley; Louis H. Miller
• Keywords: Lymphokines; Erythrocytes; Chemotactic Factors; Chemokine CXCL1; Interleukin-8; Protozoan Proteins; Antigens, Protozoan; Receptors, Cell Surface; Monocyte Chemoattractant Proteins; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Animals; Cytokines; Humans; Intercellular Signaling Peptides and Proteins; Plasmodium knowlesi; Receptors, Immunologic; Duffy Blood-Group System; Growth Substances; Plasmodium vivax; Chemokine CCL5; Chemokines, CXC

Plasmodium vivax and P. falciparum are the major causes of human malaria, except in sub-Saharan Africa where people lack the Duffy blood group antigen, the erythrocyte receptor for P. vivax . Duffy negative human erythrocytes are resistant to invasion by P. vivax and the related monkey malaria, P. knowlesi . Several lines of evidence in the present study indicate that the Duffy blood group antigen is the erythrocyte receptor for the chemokines interleukin-8 (IL-8) and melanoma growth stimulatory activity (MGSA). First, IL-8 binds minimally to Duffy negative erythrocytes. Second, a monoclonal antibody to the Duffy blood group antigen blocked binding of IL-8 and other chemokines to Duffy positive erythrocytes. Third, both MGSA and IL-8 blocked the binding of the parasite ligand and the invasion of human erythrocytes by P. knowlesi , suggesting the possibility of receptor blockade for anti-malarial therapy.