Head David J, Lee Zoe E, Poole Joyce, Avent Neil D
Genomics Research Institute and Centre for Research in Biomedicine, University of the West of England, Bristol, Frenchay, Bristol, UK.
Br J Haematol. 2005 Apr;129(1):130-7. doi: 10.1111/j.1365-2141.2005.05407.x.
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.
血型糖蛋白C（GPC）是一种在红细胞上表达的40 kDa糖蛋白，是疟原虫恶性疟原虫侵入这些细胞的受体。疟原虫感染红细胞上GPC的出现提示了GPC结合（连接）与红细胞上磷脂酰丝氨酸（PS）表达之间的联系。磷脂酰丝氨酸表达也已被证明是包括红细胞中一些在内的多种生物学途径中细胞死亡的标志物。使用膜联蛋白V结合，我们证明GPC与小鼠单克隆抗体（BRIC-10）连接可诱导正常红细胞上PS的表达。完整红细胞经胰蛋白酶消化后可防止磷脂酰丝氨酸暴露。此外，表达截短细胞外结构域的GPC变异表型Yus（缺失外显子2）和Gerbich（缺失外显子3）在与BRIC-10结合后不表达PS，而PS在Ls(a)红细胞（外显子3重复）上暴露。体外培养24小时后，GPC连接还导致野生型红细胞的活力随之丧失。这些结果确定了一条将GPC与红细胞上PS暴露联系起来的潜在途径，这可能在调节红细胞更新中起作用。对该途径的进一步表征也可能确定治疗恶性疟原虫疟疾的新靶点。
