Ramacciotti Eduardo, Hawley Angela E, Farris Diana M, Ballard Nicole E, Wrobleski Shirley K, Myers Daniel D, Henke Peter K, Wakefield Thomas W
Conrad Jobst Vascular Research Laboratories, Section of Vascular Surgery, University of Michigan Medical School Center, Ann Arbor, MI, USA.
Thromb Haemost. 2009 Apr;101(4):748-54.
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 wild-type, 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 (DeltaCT). 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 MPs derived from platelets for WT animals (p < 0.05), while MPs from platelets presented a positive correlation to thrombus weight in the WT and EPKO groups (p < 0.01). Total MPs correlated negatively with thrombus weight in the DeltaCT group (p < 0.05). MP re-injections led to greater thrombus weight, while older MP reinjections tended to form larger thrombus than younger. Finally, TF bearing MPs showed a significant correlation to MP concentrations (R = 0.99). In conclusion, MPs appear to be an important element in venous thrombogenesis.
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。我们评估了在野生型小鼠、E-选择素和P-选择素基因缺失小鼠以及静脉血栓形成起始后P-选择素表达水平高的小鼠中,微粒对血栓形成及相关组织因子(TF)活性的详细时间进程分析。对C57BL/6小鼠(n = 191,59只 = 野生型[WT],55只 = E-选择素和P-选择素基因缺失[基因敲除,EPKO],77只 = 可溶性P-选择素水平升高,称为Delta细胞质尾[DeltaCT])进行下腔静脉(IVC)结扎。在不同时间点对动物实施安乐死,以评估微粒的产生、来源和血栓重量。将微粒以80,000和160,000单位的浓度以及不同年龄重新注射到单独的小鼠体内。此外,将来自形成血栓动物的微粒汇集起来,使用显色测定法定量TF活性。对于野生型动物,血栓重量与源自白细胞的微粒呈负相关,与源自血小板的微粒呈正相关(p < 0.05),而在野生型和EPKO组中,源自血小板的微粒与血栓重量呈正相关(p < 0.01)。在DeltaCT组中,总微粒与血栓重量呈负相关(p < 0.05)。重新注射微粒导致血栓重量增加,而注射较老的微粒往往比注射较年轻的微粒形成更大的血栓。最后,携带TF的微粒与微粒浓度呈显著相关性(R = 0.99)。总之,微粒似乎是静脉血栓形成中的一个重要因素。