STIMULATION OF THE ADHERENCE OF NEUTROPHILS TO UMBILICAL VEIN ENDOTHELIUM BY HUMAN RECOMBINANT TUMOR-NECROSIS-FACTOR
STIMULATION OF THE ADHERENCE OF NEUTROPHILS TO UMBILICAL VEIN ENDOTHELIUM BY HUMAN RECOMBINANT TUMOR-NECROSIS-FACTOR
复制标题
DOI：
10.1073/pnas.82.24.8667
复制
发表时间：
1985-12-01
影响因子：
11.1
通讯作者：
VADAS, MA
中科院分区：
文献类型：
--
作者：
GAMBLE, JR;HARLAN, JM;VADAS, MA
重组人肿瘤坏死因子（TNF）在体外被发现可增强人外周血中性粒细胞对人脐静脉内皮细胞（HUVE）单层的黏附。这种增强作用是由于对中性粒细胞和HUVE细胞两者的影响。对中性粒细胞的作用在5分钟内达到最大诱导程度，且不需要蛋白质或RNA合成。相比之下，对HUVE细胞的最大作用需要4小时才能形成，并且需要从头进行蛋白质和RNA合成；然而，HUVE细胞暴露于TNF仅5分钟就足以引发变化，导致在4小时时中性粒细胞的最大黏附。针对TNF的单克隆抗体可阻断对中性粒细胞和对HUVE细胞的作用。TNF还能迅速诱导中性粒细胞表面一种糖蛋白抗原表达增加，该糖蛋白是最佳黏附和补体成分C3bi受体（CR3）功能所必需的，这种抗原可被针对其表位的单克隆抗体所识别。因此，TNF的作用机制可能涉及细胞表面分子表达的调节。我们的观察结果表明，TNF诱导了一个对所有炎症反应发展至关重要的过程，并且血液中性粒细胞和内皮细胞都是TNF作用的靶点。TNF或TNF拮抗剂对炎症反应的调节具有广泛的临床意义。
Recombinant human tumor necrosis factor (TNF) was found to enhance the adherence of human peripheral blood neutrophils to human umbilical vein endothelial (HUVE) cell monolayers in vitro. The enhancement was due to the effects both on neutrophils and HUVE cells. The effect on neutrophils was maximally induced within 5 min and did not require protein or RNA synthesis. By contrast, maximal effects on HUVE cells took 4 hr to develop and required de novo protein and RNA synthesis; however, exposure of HUVE cells to TNF for as little as 5 min was sufficient to initiate changes leading to maximal adherence of neutrophils at 4 hr. Both the effect on neutrophils and that on HUVE cells were blocked by a monoclonal antibody against TNF. TNF also rapidly induced an increased surface expression of neutrophil antigens recognized by monoclonal antibodies directed against epitopes of a glycoprotein required for optimum adherence and for complement component C3bi receptor (CR3) function. Thus, the mechanism of action of TNF may involve the regulation of expression of cell surface molecules. Our observations show that TNF induces a process central to the development of all inflammatory reactions and that both blood neutrophils and endothelial cells are targets of TNF action. The regulation of inflammatory reactions by TNF or antagonists of TNF has wide-ranging clinical implications.