Background/Purpose: Biliary decompression for congenital or acquired obstruction (eg, biliary atresia) does not uniformly lead to liver repair, restore function, or prevent cholangitis. The authors hypothesize that failed repair is caused by altered macrophage (Mφ) phenotypes central to an ongoing inflammatory and fibrogenic response. Methods: In adult rats, biliary obstruction was performed by suspension of the common bile duct for 5 or 7 days. Decompression followed release of the loop until death during the course of liver repair. To determine Mφ phenotype in the presence or absence of resident macrophages, animals were either administered gadolinium chloride or saline before injury and repair. At death, hepatic Mφ were isolated, stained with MAC-1 (CD11b/CD 18) and OX-3 (MHC class II), and quantified with flow cytometry. Liver sections were immunostained for ED-1 and ED2; positive Mφ were counted per square millimeter of tissue. Results: Obstruction led to bile duct proliferation, fibrosis, and inflammation. Decompression relieved jaundice and ductal hyperplasia. After injury, hepatic Mφ showed an 80% phenotypic conversion to MAC-1 and OX-3-positive cells. Cells isolated from livers at 9 days of repair persisted with 60% MAC-1 and 77% OX-3 expression. Gadolinium reduced Kupffer cells at all stages of repair. Recruited Mφ in treated animals increased 4-fold greater than controls. Conclusions: Kupffer cells appear to limit the recruitment and persistence of a systemic macrophage phenotype in liver injury and repair. Cell surface markers for systemic macrophages appear after injury and persist during repair, despite adequate biliary decompression. After biliary decompression, this macrophage phenotype accounts for inflammatory complications such as cholangitis and ongoing fibrosis.
All Science Journal Classification (ASJC) codes
- Pediatrics, Perinatology, and Child Health