Expression of phosphatidylserine (PS) on wild-type and Gerbich variant erythrocytes following glycophorin-C (GPC) ligation.
Glycophorin-C (GPC) is a 40 kDa glycoprotein expressed on erythrocytes and is a receptor for the malarial parasite Plasmodium falciparum to invade these cells. A link between GPC binding (ligation) and phosphatidylserine (PS) expression on erythrocytes has been suggested by its appearance on P. falciparum-infected erythrocytes. Phosphatidylserine expression has also been shown to be a marker of cellular death in a number of biological pathways including some in erythrocytes. Using Annexin V binding, we demonstrated that ligation of GPC with mouse mAb (BRIC-10) induced PS expression on normal erythrocytes. Phosphatidylserine exposure was prevented following tryptic digestion of intact erythrocytes. In addition, GPC variant phenotypes Yus (Delta exon 2) and Gerbich (Delta exon 3), which express a truncated extracellular domain, did not express PS following BRIC-10 binding, whereas PS was exposed on Ls(a) erythrocytes (duplication of exon 3). GPC ligation was also shown to result in a concomitant loss of erythrocyte viability in wild-type erythrocytes after 24 h in vitro. These results identify a potential pathway linking GPC to PS exposure on erythrocytes that may have a role in regulating red cell turnover. Further characterization of this pathway may also identify new targets for the treatment of P. falciparum malaria.
Head
David J
DJ
Genomics Research Institute and Centre for Research in Biomedicine, University of the West of England, Bristol, Frenchay, Bristol, UK.
Lee
Zoe E
ZE
Poole
Joyce
J
Avent
Neil D
ND
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D001789:Blood Group Antigens / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D004913:Erythrocytes, Abnormal / Q000378:metabolism; D006021:Glycophorins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010718:Phosphatidylserines / Q000378:metabolism*; D014357:Trypsin / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D001789:Blood Group Antigens; D006021:Glycophorins; D010718:Phosphatidylserines; D014357:Trypsin