Role of hepatic resident and infiltrating macrophages in liver repair after acute injury.

Authors:
Qiang You
Qiang You
University of Colorado Health Sciences Center
United States
Michael Holt
Michael Holt
University of Colorado Denver
United States
Hao Yin
Hao Yin
David H. Koch Institute for Integrative Cancer Research
Cambridge | United States
Guiying Li
Guiying Li
Guangzhou Institute of Geochemistry
China
Dr. Cheng-Jun Hu, PhD
Dr. Cheng-Jun Hu, PhD
University of Colorado
Associate Professor
Pulmonary hypertension
Aurora, CO | United States
Cynthia Ju
Cynthia Ju
University of Colorado Health Sciences Center
United States

Biochem Pharmacol 2013 Sep 19;86(6):836-43. Epub 2013 Jul 19.

Department of Biotherapy, Second Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210011, China.

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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Source
http://dx.doi.org/10.1016/j.bcp.2013.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3863645PMC
September 2013
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32 Citations
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