Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1.
Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1.
复制标题
DOI：
10.1084/jem.163.6.1363
复制
发表时间：
1986-06-01
期刊：
影响因子：
--
通讯作者：
Stern D
中科院分区：
文献类型：
--
作者：
Nawroth PP;Bank I;Handley D;Cassimeris J;Chess L;Stern D
肿瘤坏死因子/恶病质素（TNF）已被牵连作为一个介导的宿主反应，脓毒症和肿瘤。最近的研究表明，TNF可以调节内皮细胞止血特性，表明内皮是TNF的靶组织。这使我们研究内皮细胞是否具有TNF的特异性结合位点，并通过阐述炎症介质IL-1来增强对TNF的生物反应。125 I-重组人TNF与融合的培养的人脐静脉内皮细胞孵育导致时间依赖性、可逆性和饱和性结合。在TNF浓度为105 +/- 40 pM时，结合为半最大值，在饱和时，每个细胞结合1，500个分子。热处理的TNF没有生物活性，不与内皮结合。除了表面结合，TNF诱导的IL-1活性的阐述内皮细胞在一个时间依赖性的方式。IL-1活性的产生需要蛋白质合成，并且在TNF浓度为50 +/- 20 pM时达到最大值的一半。IL-1活性从TNF-处理的内皮细胞可以吸附的固定化抗体的IL-1。热处理的TNF在诱导内皮细胞IL-1方面无效。这些数据表明，TNF可以特异性结合内皮细胞，并启动血管表面上的炎症和凝血事件的级联反应，可能是宿主对肿瘤和脓毒症的反应的核心。
Tumor necrosis factor/cachectin (TNF) has been implicated as a mediator of the host response in sepsis and neoplasia. Recent work has shown that TNF can modulate endothelial cell hemostatic properties, suggesting that endothelium is a target tissue for TNF. This led us to examine whether endothelial cells have specific binding sites for TNF and augment the biological response to TNF by elaborating the inflammatory mediator, IL-1. Incubation of 125I-recombinant human TNF with confluent, cultured human umbilical vein endothelial cells resulted in time-dependent, reversible, and saturable binding. Binding was half-maximal at a TNF concentration of 105 +/- 40 pM, and at saturation 1,500 molecules were bound per cell. Heat-treated TNF, which is biologically inactive, did not bind to endothelium. In addition to surface binding, TNF induced the elaboration of IL-1 activity by endothelial cells in a time-dependent manner. Generation of IL-1 activity required protein synthesis and was half-maximal at a TNF concentration of 50 +/- 20 pM. IL-1 activity from TNF-treated endothelium could be adsorbed by an immobilized antibody to IL-1. Heat- treated TNF was ineffective in eliciting endothelial cell IL-1. These data indicate that TNF can bind specifically to endothelium and initiate a cascade of inflammatory and coagulant events on the vessel surface potentially central to the host response to neoplasia and sepsis.