Kopp C W, Robson S C, Siegel J B, Anrather J, Winkler H, Grey S, Kaczmarek E, Bach F H, Geczy C L
Sandoz Center for Immunobiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Thromb Haemost. 1998 Mar;79(3):529-38.
The regulation of tissue factor (TF) activity by the cell associated tissue factor pathway inhibitor (TFPI) during monocyte (Mo) and endothelial cell (EC) interactions is not fully understood. This report describes co-ordinate induction of TF antigen (TF-Ag) and membrane-associated TFPI-Ag on human Mo following coculture with human aortic (HAEC) or porcine aortic EC (PAEC) or after stimulation with TNFalpha. We show that both allo- and xenogeneic EC induce human Mo-TF antigen in short-term culture. However, the TF activity of TNFalpha-primed Mo is suppressed when these cells are cocultured with HAEC [by 40.3 +/- 6.3% (p<0.02)] or PAEC [by 50.5 +/- 10.6% (p<0.001)]. Antibody (Ab) blocking studies confirm that TFPI is the principal anticoagulant associated with this suppression of TF-activity. Our data indicate that anti-TF activity originates, at least in part, from the activated human Mo in the coculture; additionally, specific generation of TFPI by Mo is observed under the xenogeneic culture conditions. As Mo associated TF, induced by allo- or xenogeneic EC interactions, is regulated by cell-associated TFPI, we propose that infiltrating Mo may modulate the thrombotic process at sites of vascular injury in association with both allo- and xenograft rejection.
单核细胞（Mo）与内皮细胞（EC）相互作用期间，细胞相关组织因子途径抑制剂（TFPI）对组织因子（TF）活性的调节作用尚未完全明确。本报告描述了人Mo与人类主动脉内皮细胞（HAEC）或猪主动脉内皮细胞（PAEC）共培养后，或经肿瘤坏死因子α（TNFα）刺激后，TF抗原（TF-Ag）和膜相关TFPI-Ag的协同诱导情况。我们发现，同种和异种EC在短期培养中均可诱导人Mo-TF抗原。然而，当TNFα预处理的Mo与HAEC [抑制40.3±6.3%（p<0.02）]或PAEC [抑制50.5±10.6%（p<0.001）]共培养时，其TF活性受到抑制。抗体（Ab）阻断研究证实，TFPI是与这种TF活性抑制相关的主要抗凝剂。我们的数据表明，抗TF活性至少部分源自共培养中活化的人Mo；此外，在异种培养条件下观察到Mo特异性产生TFPI。由于同种或异种EC相互作用诱导的Mo相关TF受细胞相关TFPI调节，我们提出，浸润的Mo可能在同种和异种移植排斥反应中，与血管损伤部位的血栓形成过程有关。
