Tissue factor contributes to neutrophil CD11b expression in alpha-naphthylisothiocyanate-treated mice.
Tissue factor contributes to neutrophil CD11b expression in alpha-naphthylisothiocyanate-treated mice.
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DOI：
10.1016/j.taap.2010.11.002
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发表时间：
2011-02-01
影响因子：
3.8
通讯作者：
Cantor GH
中科院分区：
文献类型：
--
作者：
Luyendyk JP;Flanagan KC;Williams CD;Jaeschke H;Slusser JG;Mackman N;Cantor GH
α -萘基异硫氰酸酯（ANIT）诱导的胆汁淤积性肝损伤是由肝内胆管损伤引起的，肝坏死的进展需要促凝蛋白组织因子（TF）和肝外细胞包括中性粒细胞的参与。最近的研究表明，骨髓细胞TF有助于中性粒细胞的活化。我们验证了骨髓细胞TF对anit治疗小鼠中性粒细胞活化的作用。ANIT处理的TFflox/flox小鼠肝脏匀浆中TF活性显著增加，但在TFflox/flox/LysMCre小鼠（TFΔMyeloid小鼠）中没有，这降低了TF在单核细胞/巨噬细胞和中性粒细胞中的表达。骨髓细胞特异性TF缺乏没有改变趋化因子KC或MIP-2的表达，但根据组织髓过氧化物酶（MPO）活性显示，在48小时后，anti处理小鼠的肝脏中性粒细胞积累减少。髓系细胞TF缺乏显著降低了anit处理小鼠血液中性粒细胞CD11b的表达，这与血浆MPO蛋白水平降低有关，MPO蛋白水平是中性粒细胞脱颗粒的一个指标。然而，骨髓细胞特异性TF缺乏对anit诱导的凝血级联激活没有影响。经组织病理学和形态计量学证实，骨髓细胞TF缺乏降低了anits处理小鼠血清ALT和ALP活性的升高（p<0.05），但骨髓细胞TF缺乏并没有减少48小时肝坏死。结果表明，在胆汁淤积过程中，骨髓细胞TF通过不依赖凝血的途径参与中性粒细胞CD11b的表达。然而，由此导致的中性粒细胞积累/活化的减少不足以显著降低ANIT肝毒性，这表明骨髓细胞TF只是胆汁淤积期间调节肝坏死的众多因素之一。
Cholestatic liver injury induced by alpha-naphthylisothiocyanate (ANIT) is provoked by injury to intrahepatic bile ducts and the progression of hepatic necrosis requires the procoagulant protein tissue factor (TF) and extrahepatic cells including neutrophils. Recent studies have shown that myeloid cell TF contributes to neutrophil activation. We tested the hypothesis that myeloid cell TF contributes to neutrophil activation in ANIT-treated mice. TF activity in liver homogenates increased significantly in TFflox/flox mice treated with ANIT, but not in TFflox/flox/LysMCre mice (TFΔMyeloid mice), which have reduced TF expression in monocytes/macrophages and neutrophils. Myeloid cell-specific TF deficiency did not alter expression of the chemokines KC or MIP-2, but reduced hepatic neutrophil accumulation in ANIT-treated mice at 48 hours as indicated by tissue myeloperoxidase (MPO) activity. Myeloid cell TF deficiency significantly reduced CD11b expression by blood neutrophils in ANIT-treated mice and this was associated with reduced plasma MPO protein levels, an index of neutrophil degranulation. However, myeloid cell-specific TF deficiency had no effect on ANIT-induced coagulation cascade activation. The increase in serum ALT and ALP activities in ANIT-treated mice was reduced by myeloid cell TF deficiency (p<0.05), but the myeloid cell TF deficiency did not reduce hepatic necrosis at 48 hours, as determined by histopathology and morphometry. The results suggest that myeloid cell TF contributes to neutrophil CD11b expression during cholestasis by a coagulation-independent pathway. However, the resultant reduction in neutrophil accumulation/activation is insufficient to substantially reduce ANIT hepatotoxicity, suggesting that myeloid cell TF is only one of many factors modulating hepatic necrosis during cholestasis.
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DOI：
10.1073/pnas.77.7.4113
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BRULET, P;BABINET, C;JACOB, F
通讯作者：
JACOB, F
影响因子：
20.3
作者：
Stegenga, Michiel E.;van der Crabben, Saskia N.;van der Poll, Tom
通讯作者：
van der Poll, Tom
影响因子：
4.6
作者：
Stephenne, Xavier;Vosters, Olivier;Sokal, Etienne M.
通讯作者：
Sokal, Etienne M.
影响因子：
4.5
作者：
Ohta, Y;Kongo, M;Harada, N
通讯作者：
Harada, N
DOI：
10.1152/ajpgi.00318.2003
发表时间：
2004-03-01
影响因子：
4.5
作者：
Gujral, JS;Liu, J;Jaeschke, H
通讯作者：
Jaeschke, H