Gamble J R, Harlan J M, Klebanoff S J, Vadas M A
Proc Natl Acad Sci U S A. 1985 Dec;82(24):8667-71. doi: 10.1073/pnas.82.24.8667.
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.
重组人肿瘤坏死因子（TNF）被发现可在体外增强人外周血中性粒细胞与人脐静脉内皮（HUVE）细胞单层的黏附。这种增强是由于对中性粒细胞和HUVE细胞两者的作用。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小时才能显现，并且需要从头合成蛋白质和RNA；然而，将HUVE细胞暴露于TNF仅5分钟就足以引发导致4小时后中性粒细胞最大黏附的变化。对中性粒细胞的作用和对HUVE细胞的作用均被抗TNF单克隆抗体阻断。TNF还迅速诱导了中性粒细胞抗原的表面表达增加，这些抗原可被针对最佳黏附所需糖蛋白表位以及补体成分C3bi受体（CR3）功能的单克隆抗体识别。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诱导了所有炎症反应发展的核心过程，并且血液中的中性粒细胞和内皮细胞都是TNF作用的靶标。TNF或TNF拮抗剂对炎症反应的调节具有广泛的临床意义。
