1区 · 综合性期刊
Article
作者: Pyzik, Michal ; Rath, Timo ; Lencer, Wayne I. ; Blumberg, Richard S. ; Gandhi, Amit ; Roopenian, Derry C. ; Jones, Susan D. ; Purohit, Shalaka ; Taylor, Zachary S. ; Mizoguchi, Atsushi ; Grenha, Rosa ; Krämer, Thomas D. ; Andersen, Jan Terje ; Christianson, Greg ; Nienaber, Vicki ; Hubbard, Jonathan J. ; Sandlie, Inger ; Kuo, Timothy T. ; Baker, Kristi ; Blumberg, Laurence ; Kaplowitz, Neil ; Win, Sanda ; Mezo, Adam R. ; McDonnell, Kevin
SignificanceNeonatal crystallizable fragment receptor (FcRn) regulates immunity and homeostasis of the two most abundant circulating proteins, IgG and albumin. FcRn is expressed in hepatocytes, but hepatic FcRn function is unknown. We show that hepatic FcRn regulates albumin biodistribution. Absence of FcRn in the liver leads to hypoalbuminemia by preventing efficient albumin delivery into the circulation, causing albumin retention within hepatocytes and increasing biliary albumin excretion. Blockade of albumin–FcRn interactions protects liver from damage induced by acetaminophen, a hepatotoxin. This protection results from hepatocyte accumulation of albumin, which scavenges superoxide radicals, and from the redirection of albumin-bound acetaminophen into the bile. Therefore, FcRn-mediated homeostatic distribution of albumin into the bloodstream renders hepatocytes susceptible to acute hepatotoxin exposure, and inhibition of FcRn in the hepatocyte is protective.