M2-like macrophages in the fibrotic liver protect mice against lethal insults through conferring apoptosis resistance to hepatocytes

被引：52

作者：

Bai, Li ^{[1
]}

Liu, Xin ^{[1
]}

Zheng, Qingfen ^{[1
]}

Kong, Ming ^{[1
]}

Zhang, Xiaohui ^{[1
]}

Hu, Richard ^{[2
]}

Lou, Jinli ^{[1
]}

Ren, Feng ^{[3
]}

Chen, Yu ^{[1
]}

Zheng, Sujun ^{[1
]}

Liu, Shuang ^{[1
]}

Han, Yuan-Ping ^{[4
,5
]}

Duan, Zhongping ^{[1
,6
,7
]}

Pandol, Stephen J.

机构：

[1] Capital Med Univ, Beijing YouAn Hosp, Artificial Liver Ctr, Beijing 100069, Peoples R China

[2] Olive View UCLA Med Ctr, Los Angeles, CA 91342 USA

[3] Beijing Inst Liver Dis, Beijing 100069, Peoples R China

[4] Sichuan Univ, Coll Life Sci, Key Lab Bioresource & Ecoenvironm, Ctr Growth Metab & Aging, Chengdu 610014, Sichuan, Peoples R China

[5] Sichuan Univ, Natl Key Lab Biotherapy, Chengdu 610014, Sichuan, Peoples R China

[6] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA

[7] Dept Vet Affairs, Los Angeles, CA 90048 USA

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

基金：

中国国家自然科学基金;

关键词：

HEPATIC STELLATE CELLS; KUPFFER CELLS; FIBROSIS; INJURY; INFLAMMATION; HOMEOSTASIS; MECHANISMS; BIOMARKERS; PHENOTYPE; FAILURE;

D O I：

10.1038/s41598-017-11303-z

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Acute injury in the setting of liver fibrosis is an interesting and still unsettled issue. Most recently, several prominent studies have indicated the favourable effects of liver fibrosis against acute insults. Nevertheless, the underlying mechanisms governing this hepatoprotection remain obscure. In the present study, we hypothesized that macrophages and their M1/M2 activation critically involve in the hepatoprotection conferred by liver fibrosis. Our findings demonstrated that liver fibrosis manifested a beneficial role for host survival and apoptosis resistance. Hepatoprotection in the fibrotic liver was tightly related to innate immune tolerance. Macrophages undertook crucial but divergent roles in homeostasis and fibrosis: depleting macrophages in control mice protected from acute insult; conversely, depleting macrophages in fibrotic liver weakened the hepatoprotection and gave rise to exacerbated liver injury upon insult. The contradictory effects of macrophages can be ascribed, to a great extent, to the heterogeneity in macrophage activation. Macrophages in fibrotic mice exhibited M2-preponderant activation, which was not the case in acutely injured liver. Adoptive transfer of M2-like macrophages conferred control mice conspicuous protection against insult. In vitro, M2-polarized macrophages protected hepatocytes against apoptosis. Together, M2-like macrophages in fibrotic liver exert the protective effects against lethal insults through conferring apoptosis resistance to hepatocytes.

引用

页数：12

共 41 条

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