Epitope specific induction of proteinuria by monoclonal antibodies.

Epitope specific induction of proteinuria by monoclonal antibodies.
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单克隆抗体表位特异性诱导蛋白尿。

DOI:
10.1038/ki.1988.74
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发表时间:
1988
影响因子:
19.6
通讯作者:
Rennke,HG
Rennke,HG
中科院分区:
医学1区
文献类型:
--
作者:
Mendrick,DL;Rennke,HG

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二.单克隆抗体对蛋白尿的表位特异性诱导。针对大鼠肾小球中存在的新型上皮细胞表面唾液酸糖蛋白SGP-115/107的单克隆抗体K9/9已显示在体内给药后诱导肾小球上皮细胞消失和收缩以及蛋白质排泄率增加。这种损伤在给予识别这种上皮细胞抗原但具有不同表位特异性的两种另外的单克隆抗体后未观察到。为了进一步阐明上皮细胞异常的机制,对原代培养中建立的肾小球上皮细胞进行体外研究。这些抗体中没有一个单独出现在培养的细胞中诱导改变。然而,IgG 2a同种型的抗体在体外诱导补体依赖性细胞损伤,尽管当在完整动物中施用时未能致病。K9/9的致病潜力不能归因于其同种型或与抗原结合或解离的速率。研究表明,所有三种单克隆抗体识别SGP-115/107上不同但空间上接近的表位。这些结果表明,第一次,补体和白细胞的组织损伤,从单克隆抗体和其特定的,上皮细胞表面抗原之间的表位特异性相互作用的结果的独立机制。在其他细胞系统中获得的结果表明,上皮细胞结构和功能的异常可能是由特定细胞表面成分,特别是生长因子受体和模拟特定激动剂作用的单克隆抗体之间的相互作用引起的。
II. Epitope specific induction of proteinuria by monoclonal antibodies. A monoclonal antibody, K9/9, directed against a novel epithelial cell surface sialo-glycoprotein, SGP-115/107, present in the rat glomerulus, has been shown to induce glomerular epithelial cell effacement and retraction, and an increase in protein excretion rate upon in vivo administration. Such damage is not seen upon administration of two additional monoclonal antibodies that recognize this epithelial cell antigen, but with different epitope specificities. To further clarify the mechanism of the epithelial cell abnormality, in vitro studies were performed on glomerular epithelial cells established in primary culture. None of these antibodies alone appeared to induce alterations in the cultured cells. However, an antibody of the IgG2aisotype induced complement-dependent cell damage in vitro, although failed to be pathogenic when administered in the intact animal. The pathogenic potential of K9/9 cannot be attributed to its isotype or rates of association or dissociation from the antigen. Studies suggest that all three monoclonal antibodies recognize different, though spatially close epitopes on SGP-115/107. These results demonstrate, for the first time, a complement- and leukocyte-independent mechanism of tissue injury that results from an epitope-specific interaction between a monoclonal antibody and its specific, epithelial cell surface-antigen. Results obtained in other cell systems suggest that abnormalities of epithelial cell structure and function can result from the interaction between specific cell surface components, particularly growth factor receptors, and monoclonal antibodies that mimic the actions of the specific agonist.
DOI: 10.1073/pnas.77.9.5419
发表时间: 1980-01-01
期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子: --
作者:
KROLICK, KA;VILLEMEZ, C;VITETTA, ES
通讯作者: VITETTA, ES
针对表皮生长因子受体的单克隆抗体诱导表皮生长因子的早期和延迟效应。
DOI: 10.1073/pnas.78.12.7535
发表时间: 1981
影响因子: 11.1
作者:
Schreiber,AB;Lax,I;Yarden,Y;Eshhar,Z;Schlessinger,J
通讯作者: Schlessinger,J
DOI: 10.1172/jci110304
发表时间: 1981-01-01
影响因子: 15.9
作者:
HOLDSWORTH, SR;NEALE, TJ;WILSON, CB
通讯作者: WILSON, CB
DOI: --
发表时间: 1979
影响因子: 7.8
作者:
Michael Chinkers;J. Mckanna;S. Cohen
通讯作者: S. Cohen
针对大鼠肾小球抗原的单克隆抗体:生产和特异性。
DOI: --
发表时间: 1983
期刊: Laboratory investigation; a journal of technical methods and pathology
影响因子: --
作者:
Mendrick,DL;Rennke,HG;Cotran,RS;Springer,TA;Abbas,AK
通讯作者: Abbas,AK