A receptor for the malarial parasite Plasmodium vivax: the erythrocyte chemokine receptor.
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.
Horuk
R
R
Genentech, Inc., South San Francisco, CA 94080.
Chitnis
C E
CE
Darbonne
W C
WC
Colby
T J
TJ
Rybicki
A
A
Hadley
T J
TJ
Miller
L H
LH
D000818:Animals; D000953:Antigens, Protozoan; D018946:Chemokine CCL5; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004375:Duffy Blood-Group System; D004912:Erythrocytes / Q000469:parasitology*; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8 / Q000378:metabolism*; D008222:Lymphokines / Q000378:metabolism; D018945:Monocyte Chemoattractant Proteins; D016790:Plasmodium knowlesi / Q000378:metabolism* / Q000502:physiology; D010966:Plasmodium vivax / Q000378:metabolism* / Q000502:physiology; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D023062:Receptors, Interleukin-8A
D000953:Antigens, Protozoan; C475829:CXCL1 protein, human; D018946:Chemokine CCL5; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D016207:Cytokines; D004375:Duffy Blood-Group System; C066001:Duffy antigen binding protein, Plasmodium; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; D008222:Lymphokines; D018945:Monocyte Chemoattractant Proteins; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D023062:Receptors, Interleukin-8A