Lederer J A, Czuprynski C J
Department of Pathobiological Sciences, University of Wisconsin, School of Veterinary Medicine, Madison 53706.
Cytokine. 1994 Mar;6(2):154-61. doi: 10.1016/1043-4666(94)90037-x.
Our laboratory previously reported that bovine thymocytes and fibroblasts proliferated only in response to bovine IL-1, whereas proliferation of murine thymocytes was augmented equally well by murine, human, and bovine IL-1. In this study, we used direct and competitive receptor binding assays to determine whether differential binding of homologous versus heterologous IL-1 accounts for the species-specific response of bovine fibroblasts. Our results demonstrated that bovine and human fibroblasts bound homologous IL-1 with high affinity and heterologous IL-1 with lower affinity. In contrast, murine fibroblasts bound both homologous and heterologous IL-1 with high affinity. Because IL-1 and the human IL-1 receptor antagonist (IL-1ra) both bind to type 1 IL-1 receptors, we also determined whether the IL-1ra demonstrated receptor binding properties similar to human IL-1 for bovine, human, and murine fibroblasts. To our surprise, the human IL-1ra bound equally well to bovine, human and murine fibroblasts. We used this characteristic of the IL-ra to perform affinity cross-linking analysis of the IL-1 receptors on bovine, human and murine fibroblasts. These comparisons demonstrated the IL-1 receptors on bovine and human fibroblasts have similar molecular sizes (M(r) 73 kDa and M(r) kDa, respectively), whereas, IL-1 receptors on murine fibroblasts have an estimated molecular size of M(r) 88 kDa. These data demonstrate that IL-1 receptors on bovine fibroblasts preferentially bind homologous IL-1, but bovine fibroblasts do not discriminate binding by the human IL-1ra. In contrast, murine fibroblast IL-1 receptors bind heterologous IL-1 with high affinity.
我们实验室先前报道，牛胸腺细胞和成纤维细胞仅对牛白细胞介素-1（IL-1）有增殖反应，而鼠胸腺细胞的增殖在鼠、人及牛IL-1作用下均得到同等程度增强。在本研究中，我们采用直接和竞争性受体结合试验来确定同源与异源IL-1的差异结合是否可解释牛成纤维细胞的种属特异性反应。我们的结果表明，牛和人成纤维细胞以高亲和力结合同源IL-1，而以较低亲和力结合异源IL-1。相反，鼠成纤维细胞以高亲和力结合同源和异源IL-1。由于IL-1和人IL-1受体拮抗剂（IL-1ra）均与1型IL-1受体结合，我们还确定了IL-1ra对牛、人及鼠成纤维细胞是否表现出与人IL-1相似的受体结合特性。令我们惊讶的是，人IL-1ra与牛、人及鼠成纤维细胞的结合能力相同。我们利用IL-1ra的这一特性对牛、人及鼠成纤维细胞上的IL-1受体进行亲和交联分析。这些比较表明，牛和人成纤维细胞上的IL-1受体具有相似的分子大小（分别为73 kDa和 kDa），而鼠成纤维细胞上的IL-1受体估计分子大小为88 kDa。这些数据表明，牛成纤维细胞上的IL-1受体优先结合同源IL-1，但牛成纤维细胞对人IL-1ra的结合没有区分能力。相反，鼠成纤维细胞的IL-1受体以高亲和力结合异源IL-1。
