Urinary antigens as markers of papillary toxicity.: II:: Application of monoclonal antibodies for the determination of papillary antigens in rat urine

Urinary antigens as markers of papillary toxicity.: II:: Application of monoclonal antibodies for the determination of papillary antigens in rat urine
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DOI:
10.1007/s002040050612
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发表时间:
1999-06-01
影响因子:
6.1
通讯作者:
Falkenberg, FW
Falkenberg, FW
中科院分区:
医学2区
文献类型:
--
作者:
Hildebrand, H;Rinke, M;Falkenberg, FW

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我们之前报道过针对大鼠肾乳头局部抗原的特异性单克隆抗体的制备。选择与乳头状和皮质集合管上皮细胞中的抗原发生反应的三种单克隆抗体用于开发酶联免疫吸附测定(ELISA)型测定。在这些测试中确定的乳头状抗原(“PapA”)被命名为PapA1(应用单克隆抗体PapX 5C10)、PapA2(应用单克隆抗体PapX 12F6)和PapA3(应用单克隆抗体PapXI 3C7)。使用这些测定法测定大鼠尿液中的抗原排泄。根据所使用的测试化合物、施用途径和剂量,观察到的抗原释放模式有所不同。然而,在单次腹膜内施用 2-溴乙胺或丙烯亚胺后,观察到 PapA1 的释放增加,但其他两种抗原的释放没有增加,而口服施用溴乙胺的影响较小。相比之下,吲哚美辛的单次腹腔内应用或重复口服应用均导致所有三种抗原的释放增加。每日在饮食或饮用水中施用伊沙匹隆会导致尿中 PapA1 释放显着升高,并且在施用期间逐渐增加。 PapA2和PapA3的释放不受影响并保持在正常范围内。这些结果表明,随着测试的发展,异生素引起的大鼠肾乳头的变化可以通过尿液分析及早检测到,并在后续研究中进行监测。此外,应用不同化合物后获得的不同抗原释放模式表明可能存在不同的作用模式。
We have previously reported the preparation of monoclonal antibodies specific for antigens localized in the rat renal papilla. Three of the monoclonal antibodies reacting with antigens localized in papillary and cortical collecting duct epithelia were selected for the development of enzyme-linked immunosorbent assay (ELISA)-type assays. The papillary antigens ('PapA') determined in these tests were designated PapA1 (applying the monoclonal antibody PapX 5C10), PapA2 (applying the monoclonal antibody PapX 12F6), and PapA3 (applying the monoclonal antibody PapXI 3C7). Using these assays antigen excretion was determined in the urine of rats. Depending on the test compound used, the application route, and the dose, the observed antigen release patterns differed. Whereas after a single intraperitoneal application of 2-bromoethanamine or of propyleneimine an increased release of PapA1 but not of the two other antigens was observed oral application of bromoethanamine had minor effects. In contrast, both a single intraperitoneal application or repeated oral applications of indomethacin resulted in an increased release of all the three antigens. Daily application of ipsapirone in the diet or in drinking water resulted in significantly elevated urinary release of PapA1 which increased incrementally for the duration of the application. Release of PapA2 and PapA3 was not affected and remained in the normal range. These results show that with the tests developed changes in the rat renal papilla caused by xenobiotics can be detected early by urinary analysis and monitored during follow-up studies. Moreover, the different antigen release patterns obtained after application of the different compounds suggest a possible differing mode of action.