Role of hepatic resident and infiltrating macrophages in liver repair after acute injury.
Role of hepatic resident and infiltrating macrophages in liver repair after acute injury.
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DOI：
10.1016/j.bcp.2013.07.006
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发表时间：
2013-09-15
影响因子：
5.8
通讯作者：
Ju, Cynthia
中科院分区：
文献类型：
--
作者：
You, Qiang;Holt, Michael;Yin, Hao;Li, Guiying;Hu, Cheng-Jun;Ju, Cynthia
由肝毒素、病毒感染、酒精摄入或自身免疫性疾病引起的肝病的治疗仍然具有挑战性且成本高昂。肝脏具有强大的修复和再生能力，彻底了解这一精心策划的过程无疑将改善损伤后肝功能恢复的临床手段。使用过量对乙酰氨基酚（APAP）引起的急性肝损伤小鼠模型，我们的研究表明，肝脏驻留巨噬细胞（库普弗细胞，KC）和浸润巨噬细胞（IM）的缺乏导致肝脏修复明显延迟，尽管峰值肝损伤的开始和程度并未受到影响。这种延迟并不是由于肝细胞增殖受损，而是由于 APAP 诱导的肝窦内皮细胞 (LSEC) 损伤导致血管渗漏时间延长。我们还发现 KC 和 IM 表达一系列血管生成因子并诱导 LSEC 增殖和迁移。我们的机制研究表明，缺氧诱导因子（HIF）可能参与调节肝巨噬细胞（Mac）的血管生成作用，因为我们发现APAP挑战导致肝脏和肝Mac中的缺氧和HIF的稳定。总之，这些数据表明肝 Mac 在肝血管修复中发挥着重要作用，从而有助于急性损伤后的组织恢复。
Treatment of liver disease, caused by hepatotoxins, viral infections, alcohol ingestion, or autoimmune conditions, remains challenging and costly. The liver has a powerful capacity to repair and regenerate, thus a thorough understanding of this tightly orchestrated process will undoubtedly improve clinical means of restoring liver function after injury. Using a murine model of acute liver injury caused by overdose of acetaminophen (APAP), our studies demonstrated that the combined absence of liver resident macrophages (Kupffer cells, KCs), and infiltrating macrophages (IMs) resulted in a marked delay in liver repair, even though the initiation and extent of peak liver injury was not impacted. This delay was not due to impaired hepatocyte proliferation but rather prolonged vascular leakage, which is caused by APAP-induced liver sinusoidal endothelial cell (LSEC) injury. We also found that KCs and IMs express an array of angiogenic factors and induce LSEC proliferation and migration. Our mechanistic studies suggest that hypoxia-inducible factor (HIF) may be involved in regulating the angiogenic effect of hepatic macrophages (Macs), as we found that APAP challenge resulted in hypoxia and stabilization of HIF in the liver and hepatic Macs. Together, these data indicate an important role for hepatic Macs in liver blood vessel repair, thereby contributing to tissue recovery from acute injury.
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影响因子：
15.9
作者：
Fadok, VA;Bratton, DL;Henson, PM
通讯作者：
Henson, PM
DOI：
10.1073/pnas.96.26.15143
发表时间：
1999-12-21
影响因子：
11.1
作者：
Bezerra, JA;Bugge, TH;Degen, JL
通讯作者：
Degen, JL
DOI：
10.1016/j.bbrc.2006.02.143
发表时间：
2006-04-28
影响因子：
3.1
作者：
James, LP;Donahower, B;Hinson, JA
通讯作者：
Hinson, JA
影响因子：
5.5
作者：
Holt, Michael P.;Cheng, LinLing;Ju, Cynthia
通讯作者：
Ju, Cynthia
影响因子：
9.8
作者：
Bell, Beth P.;Manos, M. Michele;Sofair, Andre N.
通讯作者：
Sofair, Andre N.