牛、猪红细胞表面异种抗原改造的比较  

Comparison of Modification of Surface Xenoantigens on Bovine and Porcine Erythrocytes

作　　者：檀英霞[1] 李素波[1] 王捷熙[1] 章扬培[1] 

机构地区：[1]军事医学科学院野战输血研究所血液生化室,北京100850

出　　处：《中国实验血液学杂志》2005年第5期878-882,共5页Journal of Experimental Hematology

基　　金：国家"973"2002(B)13804项目

摘　　要：把动物红细胞输用给人,即异种输血,可以缓解目前血源紧张的矛盾,但牛和猪的红细胞与人的血浆发生强烈的凝集反应,不能直接输用。本研究首次对牛和猪红细胞表面抗原进行修饰改造,并对改造后的猪、牛红细胞进行比较,从而为开拓丰富来源、安全有效的人血代用品奠定基础。使用基因重组的咖啡豆α半乳糖苷酶清除牛和猪红细胞表面的主要异种抗原αGal抗原,结合使用化学材料甲氧基聚乙二醇(mPEG)修饰遮蔽牛和猪红细胞表面的非主要异种抗原nonαGal抗原,以实现对牛和猪红细胞表面异种抗原的改造。结果:改造后的牛、猪红细胞与人混合血浆的盐水凝集反应消失,具有和人红细胞相似的血清学特征;牛红细胞比猪红细胞脆性低,异种抗原的表达量低,及其他的一些特征说明牛红细胞比猪红细胞更适合作为人红细胞代用品。结论:改造后的牛红细胞与人血浆相匹配,有可能成为人红细胞代用品。This study was aimed to explore impact of removal of cell membrane Galα1-3Gailβ-4Glc NAc epitopes （ called α-Gal） and chemical modification of other xenoantigen on bovine red blood cell （ bRBC ） and porcine red blood cell （pRBC） antigenicity and to compare thier modified erythrocytes, in order to provide basis for development of human blood substitute with rich source, high safety and efficacy, bRBC and pRBC were subjected to both enzymatic removal of membrane α-Gal with recombinant coffee bean α-galactosidase （rCα-GalE） and covalent attachment of benzotriazole carbonate-linked methoxypolyethylene glycol （mPEG-BTC, MW =20 kD）. The effects of treatment were measured by hemagglutination, flow cytometric assay of IgG binding and clinical cross-match testing to human sera. The results showed that although α-galactosidase treatment reduced hemagglutination titers to levels similar to negative control, the combination of the treatments was most effective. Clinically used cross-match tests between bRBC, pRBC and human sera demonstrated increased compatibility. Bovine RBC were more robust than pRBC, and had less xenoantigens, and had longer half life than pRBC in vivo. These characteristics suggested that bRBCs were more suitable to investigation as an alternatives to hRBC in clinical transfusion than pRBC. These data suggested that strategies to remove or mask xenoantigens on bRBC reduce antigenicity sufficiently to allow in vitro cross-match compatibility to human sera, and therefore bRBC following modification may be considered as human blood substitut.

关 键 词：牛红细胞 猪红细胞 异种抗原 抗原改造 异种输血 

分 类 号：R977.8[医药卫生—药品] R331.141[医药卫生—药学]