Reduced invasion and growth of Plasmodium falciparum into elliptocytic red blood cells with a combined deficiency of protein 4.1, glycophorin C, and p55.
In this investigation, we have measured the invasion and growth of the malaria parasite Plasmodium falciparum into elliptocytic red blood cells (RBCs) obtained from subjects with homozygous hereditary elliptocytosis. These elliptocytic RBCs have been previously characterized to possess molecular defects in protein 4.1 and glycophorin C. Our results show that the invasion of Plasmodium falciparum into these protein 4.1 (-) RBCs is significantly reduced. Glycophorin C (-) Leach RBCs were similarly resistant to parasite invasion in vitro. The intracellular development of parasites that invaded protein 4.1 (-) RBCs was also dramatically reduced. In contrast, no such reduction of intracellular parasite growth was observed in the glycophorin C (-) Leach RBCs. In conjunction with our recent finding that a third protein termed p55 is also deficient in protein 4.1 (-) and glycophorin C (-) RBCs, the present data underscore the importance of the membrane-associated ternary complex between protein 4.1, glycophorin C, and p55 during the invasion and growth of malaria parasites into human RBCs.
Chishti
A H
AH
Department of Biomedical Research, St. Elizabeth's Medical Center, Boston, Massachusetts 02135, USA.
Palek
J
J
Fisher
D
D
Maalouf
G J
GJ
Liu
S C
SC
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D003598:Cytoskeletal Proteins; D004612:Elliptocytosis, Hereditary / Q000097:blood / Q000235:genetics / Q000469:parasitology*; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000502:physiology; D004913:Erythrocytes, Abnormal / Q000469:parasitology*; D006021:Glycophorins / Q000172:deficiency* / Q000235:genetics; D051528:Guanylate Kinases; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D018799:Intercellular Adhesion Molecule-1 / Q000494:pharmacology; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D009479:Neuropeptides; D009703:Nucleoside-Phosphate Kinase / Q000172:deficiency* / Q000235:genetics; D010963:Plasmodium falciparum / Q000254:growth & development / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology
D003598:Cytoskeletal Proteins; D006021:Glycophorins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009479:Neuropeptides; D011994:Recombinant Proteins; C028841:erythrocyte membrane band 4.1 protein; C120557:erythrocyte membrane protein band 4.1-like 1; D018799:Intercellular Adhesion Molecule-1; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases