CD44, a signal receptor for the inhibition of the cytoadhesion of CD36-binding Plasmodium falciparum-infected erythrocytes by CSA-binding infected erythrocytes.
The cytoadhesion of Plasmodium falciparum-infected erythrocytes (IEs) in organ microvessels is a key event in the pathogenesis of cerebral malaria and pulmonary edema. Identification of the molecules involved in the interaction between IEs and endothelial cells has been a major goal of research into severe forms of malaria. In contrast, the consequences of cytoadhesion for endothelial cells have been largely ignored. By combining phenotypic selection, cytoadhesion assays and flow cytometry, we demonstrated that the cytoadhesion of CSA-binding IEs inhibited the cytoadhesion of CD36-binding IEs. We identified CD44 as a signal receptor for CSA-binding IEs cytoadhesion, and demonstrated that the signal was transduced to CD36 through a pathway involving the Src-kinase family and MEK. CD36-mediated cytoadhesion was modulated independently of changes in CD36 expression. These results provide the first evidence that some IEs can downregulate the cytoadhesion of IEs of another phenotype, by modifying endothelial cells via a signaling pathway relating CD44 to CD36. Mimicking this phenomenon may constitute an interesting therapeutic strategy for inhibiting the adhesion of CD36-binding IEs -- the most abundant phenotype among field isolates -- and promoting their degradation in the spleen.
Jurzynski
Christophe
C
Unité de Parasitologie Expérimentale, EA3282 Institut Pasteur/Univ. Med., IFR48, Faculté de Médecine de la Timone, 27 Boulevard Jean Moulin, 13385 Marseille, France.
Gysin
Jürg
J
Pouvelle
Bruno
B
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000166:cytology; D018955:CD36 Antigens / Q000378:metabolism*; D002448:Cell Adhesion; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology* / Q000502:physiology*; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008168:Lung / Q000098:blood supply / Q000166:cytology; D012453:Saimiri; D015398:Signal Transduction
D018955:CD36 Antigens; D018960:Hyaluronan Receptors; D002809:Chondroitin Sulfates