Bichler K H, Kleinknecht S, Nelde H J, Strohmaier W L
Department of Urology, University of Tübingen, FRG.
Urol Res. 1991;19(6):367-73. doi: 10.1007/BF00310152.
The use of tumor necrosis factor (TNF) in immunotherapy of tumor diseases has attracted increasing interest. Since the direct antitumor effect of the TNF is mediated by receptor-bound TNF, we immunohistologically stained both benign and malignant tissue from 35 tumor-bearing human kidneys for TNF. Using a polyclonal anti-TNF-antiserum, paraffin sections were tested in the presence and absence of in vitro preincubation with TNF. Furthermore, all specimens were stained immunohistologically for Tamm-Horsfall protein (THP) because this renospecific glycoprotein can bind TNF in a lectin-like manner. In the absence of TNF preincubation, malignant tissue was TNF-positive in 34 specimens, as was benign tissue from the same tumor-bearing kidneys in 35 cases. In several specimens the staining was so intense that preincubation with TNF did not enhance the reaction. Whereas TNF staining in tumor tissue was relatively homogenous, that in benign tissue was intensive in distal tubuli, moderate in proximal tubuli, and negative in glomeruli. THP staining was negative in malignant kidney tissue but positive in the distal tubuli of benign tissue, i.e., in the regions in which TNF staining was most intense. These results indicate that TNF binds not only to membrane, most likely in a receptor-mediated manner, but also to THP both in vivo and in vitro. In vivo binding of TNF to THP was confirmed in animal experiments in which pigs were given injections of TNF. Immunohistological staining of the animals' kidneys revealed positive reactions for both TNF and THP at the distal tubuli, indicating TNF binding to THP after in vivo TNF administration.(ABSTRACT TRUNCATED AT 250 WORDS)
肿瘤坏死因子(TNF)在肿瘤疾病免疫治疗中的应用已引起越来越多的关注。由于TNF的直接抗肿瘤作用是由受体结合型TNF介导的,我们对35例患肿瘤的人肾的良性和恶性组织进行了TNF免疫组织化学染色。使用多克隆抗TNF抗血清,对石蜡切片在有无TNF体外预孵育的情况下进行检测。此外,所有标本均进行了Tamm-Horsfall蛋白(THP)免疫组织化学染色,因为这种肾特异性糖蛋白能以凝集素样方式结合TNF。在没有TNF预孵育的情况下,34份标本中的恶性组织TNF呈阳性,来自同一患肿瘤肾脏的35例良性组织也是如此。在一些标本中,染色非常强烈,以至于TNF预孵育并未增强反应。肿瘤组织中的TNF染色相对均匀,而良性组织中的TNF染色在远端小管中强烈,在近端小管中中等,在肾小球中为阴性。THP染色在恶性肾组织中为阴性,但在良性组织的远端小管中为阳性,即在TNF染色最强烈的区域。这些结果表明,TNF不仅能以受体介导的方式与膜结合,而且在体内和体外均能与THP结合。在给猪注射TNF的动物实验中证实了TNF在体内与THP的结合。对动物肾脏进行免疫组织化学染色显示,远端小管中TNF和THP均呈阳性反应,表明在体内给予TNF后,TNF与THP结合。(摘要截短于250字)