Leukocyte- and platelet-derived microparticles correlate with thrombus weight and tissue factor activity in an experimental mouse model of venous thrombosis

Leukocyte- and platelet-derived microparticles correlate with thrombus weight and tissue factor activity in an experimental mouse model of venous thrombosis
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DOI:
10.1160/th08-09-0620
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发表时间:
2009-04-01
影响因子:
6.7
通讯作者:
Wakefield, Thomas W.
Wakefield, Thomas W.
中科院分区:
医学2区
文献类型:
--
作者:
Ramacciotti, Eduardo;Hawley, Angela E.;Wakefield, Thomas W.

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微粒(MP)是来自血小板、白细胞和内皮细胞的脂质囊泡,参与早期血栓形成。我们评估了一个详细的时间过程分析MP对血栓形成和相关的组织因子(TF)活性在野生型,在基因缺失的E-和P-选择素和高水平的P-选择素表达后,开始静脉血栓形成的小鼠。对C57 BL/6小鼠进行下腔静脉(IVC)结扎(n = 191,59 =野生型[WT],55 = E-和P -选择素的基因缺失[敲除,EPKO],77 =可溶性P-选择素水平升高,称为Delta胞质尾(Delta CT))。在不同时间点对动物实施安乐死,以评估MP产生、来源和血栓重量。MP以80,000和160,000单位的浓度以及不同年龄的浓度重新注射到单独的小鼠中。此外,合并血栓形成动物的MP,并使用显色试验定量TF活性。对于WT动物,血栓重量与白细胞来源的MP呈负相关,与血小板来源的IMP呈正相关(p
Microparticles (MP) are lipid vesicles from platelets, leukocytes and endothelial cells that are involved in early thrombogenesis. We evaluated a detailed time-course analysis of MPs on thrombogenesis and the associated tissue factor (TF) activity in wildtype, in gene-deleted for E- and P-selectins and with high levels of P-selectin expression after the initiation of venous thrombosis in mice. Inferior vena cava (IVC) ligation was performed on C57BL/6 mice (n = 191,59 = wild-type [WT], 55 = gene-deleted for E- and P - selectins [knock-outs, EPKO] and 77 = elevated levels of soluble P-selectin, named Delta Cytoplasmic Tail (Delta CT). Animals were euthanised at various time points to assess MP production, origin and thrombus weight. MPs were re-injected into separate mice at concentrations of 80,000 and 160,000 units, as well as from different ages. In addition, MPs from thrombosed animals were pooled and TF activity quantitated using a chromogenic assay. Thrombus weight correlated negatively with MPs derived from leukocytes, and positively with IMPs derived from platelets for WT animals (p