C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor.
C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor.
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DOI：
10.1182/blood.v82.2.513.bloodjournal822513
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发表时间：
1993
期刊：
影响因子：
20.3
通讯作者：
J. Cermak;N. S. Key;R. R. Bach-R.;J. Balla;H. S. Jacob;G. Vercellotti
中科院分区：
文献类型：
--
作者：
J. Cermak;N. S. Key;R. R. Bach-R.;J. Balla;H. S. Jacob;G. Vercellotti
急性炎症反应常伴有严重的血栓事件。我们发现c反应蛋白（CRP），一种急性期反应物，在炎症刺激下显著增加其血清浓度，诱导单核细胞表达组织因子（TF），一种有效的促凝剂。体内炎症期间通常达到的纯化人CRP浓度（10至100微克/毫升）诱导人外周血单核细胞（PBM）的TF促凝活性（PCA）增加75倍，同时TF抗原水平平行增加。crp诱导的PCA被一种人源性TF单克隆抗体完全阻断，而不被无关的小鼠IgG阻断。Dot blot分析显示，与CRP孵育4小时后，TF mRNA显著升高，PCA在6、8小时内达到峰值。放线菌素D和环己亚胺阻断了crp刺激的PCA，表明需要重新合成TF蛋白。排除内毒素（LPS）污染的CRP作为TF合成的中介，因为：(1)CRP是鲎试验阴性；(2)与lps诱导的PCA相比，CRP诱导的TF PCA不被多粘菌素B阻断；(3)抗人CRP IgG对CRP诱导的PCA有抑制作用，但对lps诱导的PCA无抑制作用；(4)在LPS预处理的PBM中，CRP能够刺激TF的产生；(5)与LPS不同，CRP不能在人脐静脉内皮细胞中诱导TF。我们认为，单核细胞中crp介导的TF产生可能有助于炎症状态下弥散性血管内凝血和血栓形成的发展。
The acute inflammatory response is frequently accompanied by serious thrombotic events. We show that C-reactive protein (CRP), an acute-phase reactant that markedly increases its serum concentration in response to inflammatory stimuli, induced monocytes to express tissue factor (TF), a potent procoagulant. Purified human CRP in concentrations commonly achieved in vivo during inflammation (10 to 100 micrograms/mL) induced a 75-fold increase in TF procoagulant activity (PCA) of human peripheral blood mononuclear cells (PBM), with a parallel increase in TF antigen levels. CRP-induced PCA was completely blocked by a monoclonal antibody against human TF but not by irrelevant murine IgG. Dot blot analysis showed a significant increase of TF mRNA after 4 hours of incubation with CRP, followed by a peak of PCA within 6 and 8 hours. Actinomycin D and cycloheximide blocked CRP-stimulated PCA, suggesting that de novo TF protein synthesis was required. Endotoxin (LPS) contamination of CRP was excluded as the mediator of TF synthesis because: (1) CRP was Limulus assay negative; (2) induction of TF PCA by CRP was not blocked by Polymyxin B, in contrast to LPS-induced PCA; (3) antihuman CRP IgG inhibited CRP-induced PCA, but not LPS-induced PCA; (4) CRP was able to stimulate TF production in LPS-pretreated PBM refractory to additional LPS stimulation; and, (5) unlike LPS, CRP was incapable of inducing TF in human umbilical vein endothelial cells. We suggest that CRP-mediated TF production in monocytes may contribute to the development of disseminated intravascular coagulation and thrombosis in inflammatory states.