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用双特异性抗-D×抗-FcγRIII Fab片段致敏的红细胞通过FcγRIII激活人K细胞和腹腔巨噬细胞的能力比较。

Comparison of the ability of red cells sensitized with a bispecific anti-D x anti-Fc gamma RIII Fab fragment to activate human K cells and peritoneal macrophages through Fc gamma RIII.

作者信息

Bakács T, Hadley A G, Kumpel B M, Segal D M, Banhidy F

机构信息

National Institute of Oncology, Budapest, Hungary.

出版信息

Immunol Lett. 1994 Sep;42(1-2):91-5. doi: 10.1016/0165-2478(94)90041-8.

DOI:10.1016/0165-2478(94)90041-8
PMID:7829136
Abstract

The functional activity of Fc gamma RIII on human K cells from peripheral blood was compared with that of Fc gamma RIII on peritoneal macrophages (PM) separated from the waste material of patients undergoing peritoneal dialysis. Fc gamma R function was assessed in vitro using human monoclonal IgG1 anti-D (AB5) or a bispecific antibody comprising Fab fragments of AB5 chemically linked to Fab fragments of monoclonal anti-Fc gamma RIII, 3G8 (AB5 x 3G8). In antibody-dependent cell-mediated cytotoxicity (ADCC) assays, K cells mediated the lysis of papainized red cells sensitized with the AB5 x 3G8 bispecific antibody but not with AB5. In contrast, red cell lysis by PM was not promoted by AB5 x 3G8 although AB5 was active. However, this lysis, being inhibited by monomeric IgG, was presumably mediated via Fc gamma RI. AB5 x 3G8 also failed to promote the binding and phagocytosis of both papainized and native red cells by PM although 99% of red cells and over 90% of peritoneal cells bound the bispecific antibody. In marked contrast to K cells therefore, Fc gamma RIII on PM was unable to mediate functional interactions with red cells sensitized with anti-D x anti-Fc gamma RIII bispecific antibody.

摘要

将来自外周血的人K细胞上FcγRIII的功能活性与从接受腹膜透析患者的废料中分离出的腹膜巨噬细胞(PM)上FcγRIII的功能活性进行了比较。使用人单克隆IgG1抗-D(AB5)或一种双特异性抗体在体外评估FcγR功能,该双特异性抗体由化学连接至单克隆抗FcγRIII的Fab片段3G8(AB5×3G8)的AB5的Fab片段组成。在抗体依赖性细胞介导的细胞毒性(ADCC)试验中,K细胞介导了用AB5×3G8双特异性抗体而非AB5致敏的木瓜蛋白酶处理的红细胞的裂解。相反,尽管AB5有活性,但AB5×3G8并未促进PM对红细胞的裂解。然而,这种裂解被单体IgG抑制,推测是通过FcγRI介导的。AB5×3G8也未能促进PM对木瓜蛋白酶处理的和天然红细胞的结合及吞噬作用,尽管99%的红细胞和超过90%的腹膜细胞结合了双特异性抗体。因此,与K细胞形成鲜明对比的是,PM上的FcγRIII无法介导与用抗-D×抗FcγRIII双特异性抗体致敏的红细胞的功能相互作用。

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