Human polymorphonuclear leukocytes produce and express functional tissue factor upon stimulation 1

Human polymorphonuclear leukocytes produce and express functional tissue factor upon stimulation 1
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人多形核白细胞在刺激后产生并表达功能性组织因子 1

DOI:
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发表时间:
2006
影响因子:
10.4
通讯作者:
C. Cerletti
C. Cerletti
中科院分区:
医学2区
文献类型:
--
作者:
N. Maugeri;M. Brambilla;M. Camera;A. Carbone;E. Tremoli;M. Donati;G. Gaetano;C. Cerletti

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概括。  背景:血源性组织因子(TF)在血栓形成中起着至关重要的作用。目的: 研究多形核白细胞(PMN)是否是 TF 的来源。方法和结果: 将人 PMN 与其他血细胞小心分离,并用纯化的 P-选择素或趋化肽甲酰基 MetLeuPhe (fMLP) 刺激 3 分钟:通过特异性 TF MoAb 和失活的因子 VIIa 阻断鉴定,它们表达 TF 促凝血活性;和 TF:Ag(四到六次),如流式细胞术和免疫细胞化学所示。约 40% 的透化 PMN(无论是静息状态还是刺激状态)都含有 TF:Ag,表明刺激仅改变 TF:Ag 在 PMN 中的位置。通过实时聚合酶链反应 (RT-PCR),在静息 PMN 中检测到极少量的 TF mRNA,但在用 P-选择素或 fMLP 刺激 1 小时后分别观察到 3 至 5 倍的增加。结论: 这些研究结果表明,TF 在外周 PMN 中并非组成型表达,但可以在刺激和特定基因转录时上调并产生,例如在与活化的血小板或内皮细胞接触期间。储存的 TF 在体外快速表达为活化 PMN 表面的功能分子。 PMN TF 的可用性支持炎症细胞及其与血小板相互作用导致纤维蛋白沉积和血栓形成的相关性。
Summary.  Background: Blood‐borne tissue factor (TF) plays a crucial role in thrombogenesis. Aim: To study whether polymorphonuclear leukocytes (PMN) are a source of TF. Methods and Results: Human PMN were carefully separated from other blood cells and stimulated for 3 min with purified P‐selectin or the chemotactic peptide formyl‐MetLeuPhe (fMLP): they expressed both TF procoagulant activity, as identified by specific TF MoAb and inactivated factor VIIa blockade; and TF:Ag (four to six times), as shown by flow‐cytometry and immunocytochemistry. About 40% of permeabilized PMN, both resting and stimulated, contained TF:Ag, indicating that stimulation only modifies the location of TF:Ag within PMN. By real time‐polymerase chain reaction (RT‐PCR), a very low amount of TF mRNA was detectable in resting PMN, but a 3‐ to 5‐fold increase was observed after 1‐h stimulation with P‐selectin or fMLP, respectively. Conclusions: These findings suggest that TF is not constitutively expressed in peripheral PMN, but can be up‐regulated and produced upon stimulation and specific gene transcription, as for instance during contact with activated platelets or endothelium. The stored TF is rapidly expressed in vitro as a functional molecule on the surface of activated PMN. The availability of PMN TF supports the relevance of inflammatory cells and their interaction with platelets for fibrin deposition and thrombus formation.
DOI: 10.1073/pnas.91.19.8767
发表时间: 1994-09-13
影响因子: 11.1
作者:
CELI, A;PELLEGRINI, G;FURIE, B
通讯作者: FURIE, B
DOI: 10.1016/s0741-5214(03)01033-4
发表时间: 2003-11-01
影响因子: 4.3
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通讯作者: Wakefield, TW
DOI: 10.1056/nejm199906173402418
发表时间: 1999-06
期刊: The New England journal of medicine
影响因子: --
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通讯作者: Williams Kj;I. Tabas
DOI: 10.1073/pnas.96.5.2311
发表时间: 1999-03-02
影响因子: 11.1
作者:
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通讯作者: Nemerson, Y
DOI: 10.1182/blood.v96.1.170.013k42_170_175
发表时间: 2000-07-01
期刊: BLOOD
影响因子: 20.3
作者:
Rauch, U;Bonderman, D;Nemerson, Y
通讯作者: Nemerson, Y