Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration.
Vascular permeability factor: a tumor-derived polypeptide that induces endothelial cell and monocyte procoagulant activity, and promotes monocyte migration.
复制标题
DOI：
10.1084/jem.172.6.1535
复制
发表时间：
1990-12-01
期刊：
影响因子：
--
通讯作者：
Stern D
中科院分区：
文献类型：
--
作者：
Clauss M;Gerlach M;Gerlach H;Brett J;Wang F;Familletti PC;Pan YC;Olander JV;Connolly DT;Stern D
将低浓度的肿瘤坏死因子/恶病质（TNF）全身输注到携带TNF敏感性肿瘤的小鼠中，导致凝血激活、纤维蛋白形成和仅在肿瘤血管床内的闭塞性血栓形成。为了鉴定这种血管促凝血反应定位的潜在机制，已经从鼠甲基胆蒽A诱导的纤维肉瘤的上清液中将肿瘤衍生的多肽纯化至均一性，其诱导内皮组织因子合成和表达（在约300 pM处的半最大反应），并以协同方式增强对TNF的促凝血反应。基于在SDS-PAGE上的相似迁移率、同源的NH 2-末端氨基酸序列和通过豚鼠VPF的单特异性抗体的识别，该肿瘤衍生的多肽被鉴定为血管通透性因子（VPF）的鼠同源物。此外，VPF显示诱导单核细胞活化，如组织因子的表达所证明的。最后，VPF显示出诱导单核细胞趋化性穿过胶原膜和内皮细胞单层。总之，这些结果表明VPF可以调节内皮细胞和单核细胞的凝血特性，并可以促进单核细胞迁移到肿瘤床。这表明了肿瘤源性介质可以改变血管壁性质的一种机制。
Systemic infusion of low concentrations of tumor necrosis factor/cachectin (TNF) into mice that bear TNF-sensitive tumors leads to activation of coagulation, fibrin formation, and occlusive thrombosis exclusively within the tumor vascular bed. To identify mechanisms underlying the localization of this vascular procoagulant response, a tumor-derived polypeptide has been purified to homogeneity from supernatants of murine methylcholanthrene A-induced fibrosarcomas that induces endothelial tissue factor synthesis and expression (half- maximal response at approximately 300 pM), and augments the procoagulant response to TNF in a synergistic fashion. This tumor- derived polypeptide was identified as the murine homologue of vascular permeability factor (VPF) based on similar mobility on SDS-PAGE, an homologous NH2-terminal amino acid sequence, and recognition by a monospecific antibody to guinea pig VPF. In addition, VPF was shown to induce monocyte activation, as evidenced by expression of tissue factor. Finally, VPF was shown to induce monocyte chemotaxis across collagen membranes and endothelial cell monolayers. Taken together, these results indicate that VPF can modulate the coagulant properties of endothelium and monocytes, and can promote monocyte migration into the tumor bed. This suggests one mechanism through which tumor-derived mediators can alter properties of the vessel wall.