Basu Sumanta, Banerjee Debasis, Chandra Sarmila, Chakrabarti Abhijit
Biophysics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata, India.
Br J Haematol. 2008 Apr;141(1):92-9. doi: 10.1111/j.1365-2141.2008.06995.x.
This study aimed to investigate any correlation between the extent of phosphatidylserine (PS) asymmetry and sialylated glycoconjugate levels with the faster clearance of circulating erythrocytes in haemoglobin E (HbE) beta-thalassaemia. Erythrocytes from peripheral blood samples of different HbEbeta-thalassaemia patients showed loss of PS asymmetry measured by annexin V binding using flow cytometry. Maximum PS exposure was found when HbE was 50-60% and HbF was <20% indicating a possible correlation with severity of the disease. Separation of erythrocytes into aged and younger cells showed higher loss of PS asymmetry in the younger erythrocytes of HbEbeta-thalassaemia patients when compared with normal blood, where PS asymmetry was lost only in the older cells. Sialylated glycoconjugate measurement using the lectins wheatgerm agglutinin and pokeweed mitogen showed loss of sialic acid and N-acetyl-D-glucosamine-bearing glycoproteins in the order normal<homozygous E<HbEbeta-thalassaemic upon ageing. A possible correlation was found between the loss of PS asymmetry with HbE level and the reduction of glycophorins from the cell surface, mediated by membrane vesiculation. A more facilitated vesiculation process in HbEbeta-thalassaemic erythrocytes could lead to faster shedding of glycophorin-containing microvesicles, leaving highly PS-exposed erythrocytes accessible to phagocytes.
本研究旨在探讨磷脂酰丝氨酸(PS)不对称程度和唾液酸化糖缀合物水平与血红蛋白E(HbE)β地中海贫血中循环红细胞更快清除之间的相关性。使用流式细胞术通过膜联蛋白V结合测量不同HbEβ地中海贫血患者外周血样本中的红细胞,发现PS不对称性丧失。当HbE为50 - 60%且HbF < 20%时,发现PS暴露最大,这表明可能与疾病严重程度相关。将红细胞分为衰老细胞和年轻细胞,结果显示,与正常血液相比,HbEβ地中海贫血患者年轻红细胞中PS不对称性丧失更高,在正常血液中,只有衰老细胞会出现PS不对称性丧失。使用凝集素麦胚凝集素和商陆有丝分裂原进行唾液酸化糖缀合物测量,结果显示,随着细胞衰老,唾液酸和含N - 乙酰 - D - 葡萄糖胺的糖蛋白丧失情况依次为正常<纯合E<HbEβ地中海贫血。发现PS不对称性丧失与HbE水平以及细胞表面血型糖蛋白减少之间可能存在相关性,这是由膜泡形成介导的。HbEβ地中海贫血红细胞中更易发生的膜泡形成过程可能导致含血型糖蛋白的微泡更快脱落,使PS高度暴露的红细胞易被吞噬细胞识别。