Tannenbaum S H, Gralnick H R
Clinical Pathology Department, National Institutes of Health, Bethesda, MD 20892.
Blood. 1990 Jun 1;75(11):2177-84.
Endothelial cells (EC) synthesize and secrete von Willebrand factor (vWF), a multimeric glycoprotein required for normal hemostasis. Within human endothelial cells, vWF multimers of extremely high molecular weight are stored in rod-shaped organelles known as Weibel-Palade bodies. Inflammatory mediators, such as interleukin-1, induce in vitro a variety of procoagulant responses by EC, including the secretion of stored vWF. We postulated that other inflammatory mediators might act to balance this procoagulant reaction, thereby assisting in the maintenance of blood fluidity during immune activation. Both gamma-interferon (gamma-IFN) and tumor necrosis factor (TNF) were found to act independently and cooperatively to depress the stimulated release of vWF from EC. Analysis of stored vWF in either gamma-IFN and/or TNF-treated EC demonstrated a loss of high molecular weight multimers while immunofluorescent studies documented a loss of visible Weibel-Palade bodies. This suggests that gamma-IFN and TNF interfere with normal vWF storage. gamma-IFN acted in a dose-, time-, and RNA-dependent fashion, and its inhibition of vWF release was reversible with time. No effect of gamma-IFN on EC was noted when anti-serum to gamma-IFN was added. Unlike gamma-IFN, alpha-interferon did not effect EC vWF. Therefore, gamma-IFN and TNF may be important in decreasing vWF release during inflammatory or immunologic episodes.
内皮细胞（EC）合成并分泌血管性血友病因子（vWF），这是一种正常止血所需的多聚体糖蛋白。在人类内皮细胞内，极高分子量的vWF多聚体储存在称为魏尔-帕拉德小体的杆状细胞器中。炎症介质，如白细胞介素-1，在体外可诱导内皮细胞产生多种促凝血反应，包括储存的vWF的分泌。我们推测，其他炎症介质可能起到平衡这种促凝血反应的作用，从而在免疫激活过程中协助维持血液流动性。发现γ-干扰素（γ-IFN）和肿瘤坏死因子（TNF）可独立或协同作用，抑制内皮细胞受刺激后vWF的释放。对经γ-IFN和/或TNF处理的内皮细胞中储存的vWF进行分析，结果显示高分子量多聚体减少，而免疫荧光研究记录到可见的魏尔-帕拉德小体减少。这表明γ-IFN和TNF干扰了vWF的正常储存。γ-IFN以剂量、时间和RNA依赖的方式发挥作用，其对vWF释放的抑制作用随时间可逆。加入γ-IFN抗血清后，未观察到γ-IFN对内皮细胞有影响。与γ-IFN不同，α-干扰素对内皮细胞vWF无影响。因此，γ-IFN和TNF在炎症或免疫发作期间减少vWF释放方面可能很重要。
