Randolph G J, Luther T, Albrecht S, Magdolen V, Muller W A
Department of Pathology, Cornell University Medical College, New York, NY, USA.
Blood. 1998 Dec 1;92(11):4167-77.
An in vitro model consisting of endothelium grown on collagen was used to investigate how mononuclear phagocytes traverse endothelium in the basal-to-apical direction (reverse transmigration), a process that mimics their migration across vascular and/or lymphatic endothelium during atherosclerosis and resolution of inflammation, respectively. Monoclonal antibody (MoAb) VIC7 against tissue factor (TF) inhibited reverse transmigration by 77%. Recombinant tissue factor fragments containing at least six amino acids C-terminal to residue 202 also strongly inhibited reverse transmigration. TF was absent on resting monocytes but was induced on these cells after initial apical-to-basal transendothelial migration. Two additional observations suggest that TF is involved in adhesion between mononuclear phagocytes and endothelium: (1) when monocytes were incubated with lipopolysaccharide (LPS) to stimulate expression of TF before they were added to endothelium, VIC7 or soluble TF modestly inhibited their adhesion to the apical endothelial surface, each by about 35%; and (2) endothelial cells specifically bound to surfaces coated with TF fragments containing amino acids 202-219. This binding was blocked by anti-TF MoAb, suggesting that endothelial cells bear a receptor for TF. These data suggest that mononuclear phagocytes use TF, perhaps as an adhesive protein, to exit sites of inflammation.
使用一种由生长在胶原蛋白上的内皮细胞构成的体外模型，来研究单核吞噬细胞如何从基底到顶端方向穿过内皮细胞（反向迁移），这一过程分别模拟了它们在动脉粥样硬化和炎症消退过程中穿过血管和/或淋巴管内皮细胞的迁移。针对组织因子（TF）的单克隆抗体（MoAb）VIC7抑制反向迁移达77%。包含至少六个位于202位残基C末端氨基酸的重组组织因子片段也强烈抑制反向迁移。静息单核细胞上不存在TF，但在最初从顶端到基底的跨内皮迁移后，这些细胞上会诱导产生TF。另外两个观察结果表明TF参与单核吞噬细胞与内皮细胞之间的黏附：（1）当单核细胞与脂多糖（LPS）孵育以刺激TF表达后再添加到内皮细胞上时，VIC7或可溶性TF适度抑制它们与顶端内皮表面的黏附，每种抑制约35%；（2）内皮细胞特异性结合到包被有含202 - 219位氨基酸的TF片段的表面。这种结合被抗TF单克隆抗体阻断，表明内皮细胞带有TF受体。这些数据表明单核吞噬细胞利用TF，可能作为一种黏附蛋白，来离开炎症部位。
