Expression, localization, and erythrocyte binding activity of Plasmodium yoelii merozoite surface protein-8.
PyMSP-8 is a member of a family of merozoite surface proteins that have been described in Plasmodium that are characterized by the presence of a glycolipid membrane anchor and 1-2 epidermal growth factor-like domains. Immunization with recombinant PyMSP-8 has also been shown to protect mice against lethal Plasmodium yoelii malaria. In this report, we demonstrate that PyMSP-8 expression is detectable throughout the entire erythrocytic life cycle of P. yoelii 17XL, reaching peak level during trophozoite development. As determined by immunofluorescence, PyMSP-8 co-localizes with PyMSP-1 on the surface of merozoites in segmented schizonts and on the surface of ring stages in newly invaded erythrocytes. PyMSP-8 binds to the surface of uninfected mouse RBCs in a species-dependent manner, suggesting a potential role in merozoite attachment to and/or invasion of erythrocytes. The receptor for PyMSP-8 on RBCs is sensitive to trypsin digestion but is resistant to treatment with chymotrypsin or neuraminidase and is putatively identified as a approximately 105kDa membrane protein. Since PyMSP-8 binds to both mature RBCs as well as reticulocytes, it appears unlikely that the function of PyMSP-8 is restricted to the invasion of normocytes. While proper folding and conformation of PyMSP-8 are important, linear determinants of PyMSP-8 also contribute to erythrocyte binding. Unexpectedly, however, PyMSP-8 specific antibodies that are protective in vivo, do not disrupt the binding of rPyMSP-8 to its receptor on erythrocytes. The data indicate that protective anti-PyMSP-8 antibodies mediate their effect in vivo by an alternate mechanism(s).
Shi
Qifang
Q
Center for Molecular Parasitology, Department of Microbiology and Immunology, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, United States.
Cernetich-Ott
Amy
A
Lynch
Michelle M
MM
Burns
James M
JM
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology / Q000378:metabolism*; D004912:Erythrocytes / Q000469:parasitology; D007114:Immunization; D066298:In Vitro Techniques; D008288:Malaria / Q000276:immunology / Q000469:parasitology; D020066:Merozoite Surface Protein 1 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010967:Plasmodium yoelii / Q000254:growth & development / Q000276:immunology / Q000378:metabolism* / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000276:immunology / Q000378:metabolism*; D012156:Reticulocytes / Q000469:parasitology
D000953:Antigens, Protozoan; D020066:Merozoite Surface Protein 1; D015800:Protozoan Proteins; C431669:merozoite surface protein 8, Plasmodium