RECOMBINANT TUMOR-NECROSIS-FACTOR INDUCES PROCOAGULANT ACTIVITY IN CULTURED HUMAN VASCULAR ENDOTHELIUM - CHARACTERIZATION AND COMPARISON WITH THE ACTIONS OF INTERLEUKIN-1
RECOMBINANT TUMOR-NECROSIS-FACTOR INDUCES PROCOAGULANT ACTIVITY IN CULTURED HUMAN VASCULAR ENDOTHELIUM - CHARACTERIZATION AND COMPARISON WITH THE ACTIONS OF INTERLEUKIN-1
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DOI：
10.1073/pnas.83.12.4533
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发表时间：
1986-06-01
影响因子：
11.1
通讯作者：
GIMBRONE, MA
中科院分区：
文献类型：
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作者：
BEVILACQUA, MP;POBER, JS;GIMBRONE, MA
人重组肿瘤坏死因子（rTNF）被发现直接作用于培养的人血管内皮，诱导组织因子样促凝血活性（PCA）。在 rTNF（100 单位/ml）中孵育 4 小时后，从脐静脉、隐静脉、髂动脉和胸主动脉分离的连续传代内皮细胞显示，通过一阶段凝血测定测量，总细胞 PCA 显着增加（4 至 15 倍，21 次实验）。 rTNF 诱导的 PCA 也在完整的活内皮单层表面表达。 rTNF 对 PCA 的诱导具有浓度依赖性（最大 500 单位/ml）、时间依赖性、可逆性，并且可被放线菌酮和放线菌素 D 阻断，并且诱导过程中没有可检测到的内皮细胞损伤。将 rTNF 的作用与源自刺激单核细胞的天然人白细胞介素 1 (IL-1) 和两种不同种类的重组 IL-1 的作用进行比较，每种都诱导内皮 PCA。重组多肽和特异性中和抗血清的使用确立了介质的独特性质。内皮 PCA 对 TNF 和 IL-1 的反应动力学相似，表明在 .apprxeq 处迅速上升至峰值活性。 4小时，24小时下降至基础水平。与 TNF 或 IL-1 长时间孵育后 PCA 的这种特征性下降伴随着内皮细胞对最初刺激的单核因子的选择性低反应。有趣的是，发现 TNF 和 IL-1 的作用即使在单个单核因子的表观最大剂量下也是相加的。 TNF 的内皮定向作用，单独或与其他单核因子组合，可能对体内凝血和炎症反应的启动很重要。
Human recombinant tumor necrosis factor (rTNF) was found to act directly on cultured human vascular endothelium to induce a tissue factor-like procoagulant activity (PCA). After a 4-hr incubation in rTNF (100 units/ml), serially passaged endothelial cells isolated from umbilical veins, saphenous veins, iliac arteries, and thoracic aortae demonstrated a dramatic increase (4- to 15-fold, 21 experiments) in total cellular PCA as measured with a one-stage clotting assay. rTNF-induced PCA was also expressed at the surface of intact viable endothelial monolayers. Induction of PCA by rTNF was concentration dependent (maximum, 500 units/ml), time dependent, reversible, and blocked by cycloheximide and actinomycin D, and it occurred without detectable endothelial cell damage. Actions of rTNF were compared with those of natural human interleukin 1 (IL-1) derived from stimulated monocytes and two distinct species of recombinant IL-1, each of which also induced endothelial PCA. The use of recombinant polypeptides and specific neurtalizing antisera established the distinct natures of the mediators. The kinetics of the endothelial PCA responses to TNF and IL-1 were similar, demonstrating a rapid rise to peak activity at .apprxeq. 4 hr, and a decline toward basal levels by 24 hr. This characteristic decline in PCA after prolonged incubation with TNF or IL-1 was accompanied by selective endothelial hyporesponsiveness to the initially stimulating monokine. Interestingly, the effects of TNF and IL-1 were found to be additive even at apparent maximal doses of the individual monokines. Endothelial-directed actions of TNF, alone or in combination with other monokines, may be important in the initiation of coagulation and inflammatory responses in vivo.