Meager A, Sampson L E, Grell M, Scheurich P
Division of Immunobiology, National Institute for Biological Standards and Control, South Mimms, Hertfordshire, UK.
Cytokine. 1993 Nov;5(6):556-63. doi: 10.1016/s1043-4666(05)80004-3.
In this study, we investigated the type of TNF receptor expressed by the human rhabdomyosarcoma cell line KYM-1 and related TNF-sensitive sublines and showed that the majority (> 90%) of TNF receptors were type II (p75) receptors with only a relatively small number (< 10%) of type I (p55) receptors. Selection with TNF alpha led to the isolation of KYM-1 related TNF-resistant cell lines of which three cloned lines showed a near to total loss of type II TNF receptors. To investigate further the role of each type of TNF receptor in the regulation of TNF-mediated cytotoxicity and the development of TNF resistance, we used receptor-specific antibodies and antisera, able to compete with ligand binding to the respective receptor molecules, but representing efficient agonists via crosslinking of receptors. We found that in KYM-1 and related TNF-sensitive sublines both type I and type II TNF receptors can be functional on their own, as selective cross-linking of each receptor subset lead to cytolysis. However, investigation of three TNF-resistant KYM-1 related cell lines by selective receptor stimulation via cross-linking indicated different mechanisms underlied the development of TNF-resistant for each receptor type. Our data indicate that resistance to TNF-mediated cytotoxicity in KYM-1 related cell lines can be developed both by a selective loss of type II receptor expression and the selective loss of type I receptor function without reduction in type I receptor numbers.
在本研究中，我们调查了人横纹肌肉瘤细胞系KYM-1及其相关的对肿瘤坏死因子（TNF）敏感的亚系所表达的TNF受体类型，结果显示，大多数（>90%）TNF受体为II型（p75）受体，仅有相对少数（<10%）的I型（p55）受体。用肿瘤坏死因子α进行筛选，分离出了与KYM-1相关的对TNF耐药的细胞系，其中三个克隆系显示II型TNF受体近乎完全缺失。为了进一步研究每种类型的TNF受体在调节TNF介导的细胞毒性以及TNF耐药性形成中的作用，我们使用了受体特异性抗体和抗血清，它们能够与配体竞争结合各自的受体分子，但通过受体交联可作为有效的激动剂。我们发现，在KYM-1及其相关的对TNF敏感的亚系中，I型和II型TNF受体自身都可能发挥功能，因为对每个受体亚群进行选择性交联都会导致细胞溶解。然而，通过交联对三个对TNF耐药的KYM-1相关细胞系进行选择性受体刺激的研究表明，每种受体类型导致TNF耐药性形成的机制不同。我们的数据表明，KYM-1相关细胞系对TNF介导的细胞毒性产生耐药性，既可能是由于II型受体表达的选择性缺失，也可能是由于I型受体功能的选择性丧失，而I型受体数量并未减少。
