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首页> 外文期刊>Pathobiology: journal of immunopathology, molecular and cellular biology >Induction of pulmonary thromboembolism by neutrophil elastase in collagen-induced arthritis mice and effect of recombinant human soluble thrombomodulin.
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Induction of pulmonary thromboembolism by neutrophil elastase in collagen-induced arthritis mice and effect of recombinant human soluble thrombomodulin.

机译：中性粒细胞弹性蛋白酶在胶原诱导的关节炎小鼠中诱导肺血栓栓塞和重组人可溶性血栓调节蛋白的作用。

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We previously reported that during total knee arthroplasty in rheumatoid arthritis (RA) patients, the use of tourniquet might promote local release of neutrophil elastase (NE) from neutrophils, which may contribute to the development of pulmonary thromboembolism (PTE) and tissue injury. The aim of this study was to develop PTE by the use of NE in a mouse model of collagen-induced arthritis (CIA) and investigate the relationship between thrombus and endothelial cells as well as the effect of recombinant human soluble thrombomodulin (rhs-TM) in reducing the risk of PTE. Male DBA/1J mice were injected intracutaneously at several sites with an emulsion containing bovine collagen and later a booster shot to produce CIA mice. Subsequently, NE was injected intravenously 2 times a day for 3 days and after a further 4 days, mice were sacrificed. A group of mice received rhs-TM injections prior to NE injections. We divided the mice into four groups of normal, CIA control, CIA + NE, and CIA + rhs-TM + NE mice andevaluated thrombus formation status. All CIA + NE mice developed PTE. In contrast, no thrombosis was found in normal control, CIA control and CIA + rhs-TM + NE mice. Plasma thrombin level, fibrinogen expression and neutrophil count were increased in CIA + NE mice. Double staining for anticoagulant TM and procoagulant von Willebrand factor (vWF) in pulmonary endothelial cells in normal mice showed a TM-dominant expression while in both CIA control and CIA + NE mice a vWF-dominant expression compatible with coagulant status was observed. Injection of rhs-TM into CIA + NE mice resulted in a phenotypic conversion of endothelial cells from vWF-dominant to TM-dominant expression and a reduction in fibrinogen deposition. These findings demonstrate that by repeated use of NE in CIA mice, it is feasible to produce PTE and to study its pathogenesis and that rhs-TM reduces the risk of PTE. We suggest that in surgical operations of upper and lower extremities in RA patients, the use of a tourniquet should be avoided as it may trigger NE release.
机译：我们以前曾报道过在类风湿关节炎（RA）患者的全膝关节置换术中，使用止血带可能会促进中性粒细胞从中性粒细胞弹性蛋白酶（NE）的局部释放，这可能有助于发展肺血栓栓塞（PTE）和组织损伤。这项研究的目的是通过在胶原诱导性关节炎（CIA）的小鼠模型中使用NE来开发PTE，并研究血栓与内皮细胞之间的关系以及重组人可溶性血栓调节蛋白（rhs-TM）的作用在降低PTE的风险。将雄性DBA / 1J小鼠在几个部位皮内注射含有牛胶原蛋白的乳剂，随后进行加强注射以产生CIA小鼠。随后，每天两次静脉注射NE，持续3天，再过4天，处死小鼠。一组小鼠在NE注射之前接受rhs-TM注射。我们将小鼠分为正常对照组，CIA对照，CIA + NE和CIA + rhs-TM + NE小鼠四组，并评估血栓形成状态。所有CIA + NE小鼠均发生PTE。相反，在正常对照，CIA对照和CIA + rhs-TM + NE小鼠中未发现血栓形成。 CIA + NE小鼠的血浆凝血酶水平，纤维蛋白原表达和中性粒细胞计数增加。正常小鼠肺内皮细胞中抗凝剂TM和促凝剂von Willebrand因子（vWF）的双重染色显示TM为主的表达，而在CIA对照和CIA + NE小鼠中均观察到与凝血状态相容的vWF为主的表达。向CIA + NE小鼠中注射rhs-TM导致内皮细胞表型从vWF显性转化为TM显性表达，并减少了纤维蛋白原沉积。这些发现表明，通过在CIA小鼠中反复使用NE，可以生产PTE并研究其发病机理，并且rhs-TM可以降低PTE的风险。我们建议在RA患者的上肢和下肢的外科手术中，应避免使用止血带，因为它可能会触发NE释放。

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