CD36 peptides that block cytoadherence define the CD36 binding region for Plasmodium falciparum-infected erythrocytes.
Mature Plasmodium falciparum parasitized erythrocytes (PE) sequester from the circulation by adhering to microvascular endothelial cells. PE sequestration contributes directly to the virulence and severe pathology of falciparum malaria. The scavenger receptor, CD36, is a major host receptor for PE adherence. PE adhesion to CD36 is mediated by the malarial variant antigen, P. falciparum erythrocyte membrane protein 1 (PfEMP1), and particularly by its cysteine-rich interdomain region 1 (CIDR-1). Several peptides from the extended immunodominant domain of CD36 (residues 139-184), including CD36 139-155, CD36 145-171, CD36 146-164, and CD36 156-184 interfered with the CD36-PfEMP1 interaction. Each of these peptides affected binding at the low micromolar range in 2 independent assays. Two peptides, CD36 145-171 and CD36 156-184, specifically blocked PE adhesion to CD36 without affecting binding to the host receptor intercellular adhesion molecule-1 (ICAM-1). Moreover, an adhesion blocking peptide from the ICAM-1 sequence inhibits the PfEMP1-ICAM-1 interaction without affecting adhesion to CD36. These results confirm earlier observations that PfEMP1 is also a receptor for ICAM-1. Thus, the region 139-184 and particularly the 146-164 or the 145-171 regions of CD36 form the adhesion region for P. falciparum PE. Adherence blocking peptides from this region may be useful for modeling the PE/PfEMP1 interaction with CD36 and for development of potential anti-adhesion therapeutics.
Baruch
D I
DI
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. dbaruch@niaid.nih.gov
Ma
X C
XC
Pasloske
B
B
Howard
R J
RJ
Miller
L H
LH
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D018955:CD36 Antigens / Q000097:blood* / Q000737:chemistry / Q000276:immunology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D000939:Epitopes / Q000032:analysis; D004912:Erythrocytes / Q000469:parasitology* / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000276:immunology* / Q000472:pathogenicity*; D014774:Virulence
D000911:Antibodies, Monoclonal; D018955:CD36 Antigens; D000939:Epitopes; D010446:Peptide Fragments; D018799:Intercellular Adhesion Molecule-1