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2017 ; 7
(1
): 10518
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M2-like macrophages in the fibrotic liver protect mice against lethal insults
through conferring apoptosis resistance to hepatocytes
#MMPMID28874845
Bai L
; Liu X
; Zheng Q
; Kong M
; Zhang X
; Hu R
; Lou J
; Ren F
; Chen Y
; Zheng S
; Liu S
; Han YP
; Duan Z
; Pandol SJ
Sci Rep
2017[Sep]; 7
(1
): 10518
PMID28874845
show ga
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.