Activation and increase of radio-sensitive CD11b+ recruited Kupffer cells/macrophages in diet-induced steatohepatitis in FGF5 deficient mice

Nakashima, Hiroyuki; Nakashima, Masahiro; Kinoshita, Manabu; Ikarashi, Masami; Miyazaki, Hiromi; Hanaka, Hiromi; Imaki, Junko; Seki, Shu

doi:10.1038/srep34466

Cited by 36 publications

(43 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In human NASH samples, CYP7B1 expression is increased and this is believed to be an attempt by the liver to reduce hepatotoxicity during disease progression to NASH 47 . Other negatively affected genes include Adgre1 48 , Cd5l 49 , and Cd68 50 , all which are associated with NAFLD pathology. In fact, Cd68 is a typical monocyte/macrophage marker 51 , which could suggest that TAT-Gap19 has an effect on the recruitment of monocytes to the liver 52 .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of connexin hemichannels alleviates non-alcoholic steatohepatitis in mice

Willebrords

Cogliati

Pereira

et al. 2017

Sci Rep

View full text Add to dashboard Cite

While gap junctions mediate intercellular communication and support liver homeostasis, connexin hemichannels are preferentially opened by pathological stimuli, including inflammation and oxidative stress. The latter are essential features of non-alcoholic steatohepatitis. In this study, it was investigated whether connexin32 and connexin43 hemichannels play a role in non-alcoholic steatohepatitis. Mice were fed a choline-deficient high-fat diet or normal diet for 8 weeks. Thereafter, TAT-Gap24 or TAT-Gap19, specific inhibitors of hemichannels composed of connexin32 and connexin43, respectively, were administered for 2 weeks. Subsequently, histopathological examination was carried out and various indicators of inflammation, liver damage and oxidative stress were tested. In addition, whole transcriptome microarray analysis of liver tissue was performed. Channel specificity of TAT-Gap24 and TAT-Gap19 was examined in vitro by fluorescence recovery after photobleaching analysis and measurement of extracellular release of adenosine triphosphate. TAT-Gap24 and TAT-Gap19 were shown to be hemichannel-specific in cultured primary hepatocytes. Diet-fed animals treated with TAT-Gap24 or TAT-Gap19 displayed decreased amounts of liver lipids and inflammatory markers, and augmented levels of superoxide dismutase, which was supported by the microarray results. These findings show the involvement of connexin32 and connexin43 hemichannels in non-alcoholic steatohepatitis and, simultaneously, suggest a role as potential drug targets in non-alcoholic steatohepatitis.

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of connexin hemichannels alleviates non-alcoholic steatohepatitis in mice

Willebrords

Cogliati

Pereira

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Additionally, Klein et al [21] demonstrated that tissue-resident (sessile) Kupffer cells are radioresistant while monocyte-derived macrophages are radiosensitive. The CD68 + subset is also radioresistant but the CD11b + subset is radiosensitive [25] . The authors of the present study and many other investigators believe that tissueresident Kupffer cells are involved in the clearance of microorganisms while the monocyte-derived macrophages are involved in the induction of inflammation and play a role in immune surveillance [22] .…”

Section: Discussionmentioning

confidence: 99%

In vivo Lipopolysaccharide Tolerance Recruits CD11b<sup>+</sup> Macrophages to the Liver with Enhanced Bactericidal Activity and Low Tumor Necrosis Factor-Releasing Capability, Resulting in Drastic Resistance to Lethal Septicemia

Kinoshita

Miyazaki²,

Nakashima³

et al. 2017

J Innate Immun

Self Cite

View full text Add to dashboard Cite

Objectives: In vivo lipopolysaccharide (LPS) tolerance on bacterial infection was investigated, focusing on liver macrophages. Methods: LPS tolerance was induced by intraperitoneal injections with 5 μg/kg of LPS for 3 consecutive days, and then mice were intravenously infected with Escherichia coli. Results: All LPS-primed mice survived lethal bacterial infection. Drastic enhancement of bactericidal activity of liver macrophages strongly contributed to bacterial clearance. Although LPS-primed mice produced substantial amounts of tumor necrosis factor (TNF) inside the liver, TNF efflux into the systemic circulation was markedly suppressed. These mice showed a dramatic increase in CD11b⁺ monocyte- derived macrophages in the liver. The CD11b⁺ macrophages that increased in LPS-primed mice were those with strong phagocytic/bactericidal activity and an upregulated expression of Fcγ receptor I, but the subfraction with a potent TNF-producing capacity and poor phagocytic activity diminished. The adoptive transfer of CD11b⁺ macrophages from LPS-primed mice to control mice increased survival after bacterial infection and reduced the elevation of plasma TNF. LPS priming did not affect the CD68⁺ resident Kupffer cells, and CD68⁺ Kupffer cell-depleted mice still exhibited LPS tolerance with strong resistance to bacteremia. Conclusions: LPS tolerance recruits CD11b⁺ macrophages to the liver with enhanced bactericidal activity, which plays a central role in resistance to lethal bacteremia.

show abstract

“…The CD11b + mMØs were also found to accumulate in the liver following repeated lipopolysaccharide injections, but suppressed TNF efflux into the systemic circulation, thereby reducing lethal septicemia ( 60 ). In addition, the CD11b + mMØs were recruited during diet-induced steatohepatitis in FGF5 deficient mice and following partial hepatectomy, where they were crucial for liver regeneration ( 61 , 62 ). Others have observed that monocyte derived cells protect the liver from iron toxicity in hemolytic anemia by ingesting senescent and dying erythrocytes ( 63 ).…”

Section: Introduction To Macrophages In the Livermentioning

confidence: 99%

Macrophages in the Aging Liver and Age-Related Liver Disease

et al. 2018

View full text Add to dashboard Cite

The number of individuals aged 65 or older is projected to increase globally from 524 million in 2010 to nearly 1. 5 billion in 2050. Aged individuals are particularly at risk for developing chronic illness, while being less able to regenerate healthy tissue and tolerate whole organ transplantation procedures. In the liver, these age-related diseases include non-alcoholic fatty liver disease, alcoholic liver disease, hepatitis, fibrosis, and cirrhosis. Hepatic macrophages, a population comprised of both Kupffer cells and infiltrating monocyte derived macrophages, are implicated in several chronic liver diseases and also play important roles in the homeostatic functions of the liver. The effects of aging on hepatic macrophage population dynamics, polarization, and function are not well understood. Studies performed on macrophages derived from other aged sources, such as the bone marrow, peritoneal cavity, lungs, and brain, demonstrate general reductions in autophagy and phagocytosis, dysfunction in cytokine signaling, and altered morphology and distribution, likely mediated by epigenetic changes and mitochondrial defects, that may be applicable to hepatic macrophages. This review highlights recent findings in macrophage developmental biology and function, particularly in the liver, and discusses the role of macrophages in various age-related liver diseases. A better understanding of the biology of aging that influences hepatic macrophages and thus the progression of chronic liver disease will be crucial in order to develop new interventions and treatments for liver disease in aging populations.

show abstract

Activation and increase of radio-sensitive CD11b+ recruited Kupffer cells/macrophages in diet-induced steatohepatitis in FGF5 deficient mice

Cited by 36 publications

References 47 publications

Inhibition of connexin hemichannels alleviates non-alcoholic steatohepatitis in mice

Inhibition of connexin hemichannels alleviates non-alcoholic steatohepatitis in mice

In vivo Lipopolysaccharide Tolerance Recruits CD11b<sup>+</sup> Macrophages to the Liver with Enhanced Bactericidal Activity and Low Tumor Necrosis Factor-Releasing Capability, Resulting in Drastic Resistance to Lethal Septicemia

Macrophages in the Aging Liver and Age-Related Liver Disease

Contact Info

Product

Resources

About