Muzykantov V R, Smirnov M D, Zal'tsman A B, Samokhin G P
Biokhimiia. 1993 Jul;58(7):1027-32.
It was shown previously that avidin attachment to biotinylated erythrocytes induced their lysis by a homologous complement via an alternative pathway. This phenomenon hindered the use of avidin-coated immuno-erythrocytes as carriers for drug targeting. In the present work it has been demonstrated that avidin attachment to erythrocytes via a cross-linking reagent (tannin) does not induce any lysis by the complement. Tannization provides an attachment of up to 5 x 10(5) avidin molecules per erythrocyte which is commensurate with the value obtained after treatment with biotin esters. However, in contrast with biotinylated avidin-coated erythrocytes tannized cells are not lysed by the complement, while tannization itself does not diminish the erythrocyte sensitivity to lysis by the complement in the presence of activators (hemolytic antibody or activators of the alternative pathway). The avidin-induced lysis by the complement depends on the mode of avidin attachment to erythrocytes. Complement-resistant avidin-coated tannized erythrocytes bind biotinylated immunoglobulins and may therefore be used as carriers for drug targeting. The use of hemolytic antibody in biotinylated immunoglobulins attached to avidin-coated erythrocytes provides their controlled lysis by a complement activated via a classical pathway.
先前的研究表明,抗生物素蛋白与生物素化红细胞的结合会通过替代途径诱导同源补体使其裂解。这种现象阻碍了将抗生物素蛋白包被的免疫红细胞用作药物靶向载体。在本研究中,已证明通过交联剂(单宁)使抗生物素蛋白与红细胞结合不会诱导补体产生任何裂解。单宁化可使每个红细胞附着多达5×10⁵个抗生物素蛋白分子,这与用生物素酯处理后获得的值相当。然而,与生物素化的抗生物素蛋白包被的红细胞不同,单宁化的细胞不会被补体裂解,而单宁化本身在存在激活剂(溶血抗体或替代途径激活剂)的情况下不会降低红细胞对补体裂解的敏感性。补体介导的抗生物素蛋白诱导的裂解取决于抗生物素蛋白与红细胞的结合方式。抗补体的抗生物素蛋白包被的单宁化红细胞可结合生物素化的免疫球蛋白,因此可用作药物靶向载体。在附着于抗生物素蛋白包被的红细胞的生物素化免疫球蛋白中使用溶血抗体可使其通过经典途径激活的补体进行可控裂解。