Lantz M, Thysell H, Nilsson E, Olsson I
Department of Medicine, University Hospital, Lund, Sweden.
J Clin Invest. 1991 Dec;88(6):2026-31. doi: 10.1172/JCI115530.
Tumor necrosis factor (TNF), a protein released by activated macrophages, is a central mediator of the host response to infection and inflammation. The TNF-binding protein I (TNF-BP-I) is a soluble fragment of the p60 transmembrane TNF receptor and an antagonist to TNF. The level of serum TNF-BP-I was found to be increased in patients with renal insufficiency as a result of a decrease in the glomerular filtration rate. During hemodialysis of patients with renal failure there was a rapid but transient increase in serum TNF-BP-I. This increase was found to be caused by heparin given before dialysis and a similar dose-dependent response to heparin was observed also in healthy individuals. The finding of a repeated release of TNF-BP-I into the circulation with intermittent injections of heparin indicates that TNF-BP-I is present both in a storage pool and in a circulating pool. The mechanism for the heparin-mediated release of TNF-BP-I was not explained; TNF-BP did not show affinity for heparin. On the other hand, TNF was found to have affinity for heparin and it could also be dissociated from heparin by TNF-BP-I. It is suggested that heparin-like molecules of the extracellular matrix can retain TNF in physical proximity with target cells and restrict the actions of TNF and protect against systemic harmful manifestations.
肿瘤坏死因子（TNF）是一种由活化巨噬细胞释放的蛋白质，是宿主对感染和炎症反应的核心介质。TNF结合蛋白I（TNF-BP-I）是p60跨膜TNF受体的可溶性片段，也是TNF的拮抗剂。由于肾小球滤过率降低，肾功能不全患者血清TNF-BP-I水平升高。在肾衰竭患者血液透析期间，血清TNF-BP-I迅速但短暂升高。发现这种升高是由透析前给予的肝素引起的，并且在健康个体中也观察到对肝素类似的剂量依赖性反应。随着肝素的间歇性注射，TNF-BP-I反复释放到循环中的发现表明，TNF-BP-I既存在于储存池中，也存在于循环池中。肝素介导的TNF-BP-I释放机制尚不清楚；TNF-BP对肝素没有亲和力。另一方面，发现TNF对肝素有亲和力，并且它也可以被TNF-BP-I从肝素中解离。有人提出，细胞外基质中的肝素样分子可以使TNF与靶细胞在物理上接近，并限制TNF的作用，防止全身性有害表现。
