title: Role of splenic reservoir monocytes in pulmonary vascular monocyte accumulation in experimental hepatopulmonary syndrome.
abstract: OBJECTIVE
  Pulmonary monocyte infiltration plays a significant role in the development of angiogenesis in experimental hepatopulmonary syndrome (HPS) after common bile duct ligation (CBDL). Hepatic monocytes are also increased after CBDL, but the origins remain unclear. Splenic reservoir monocytes have been identified as a major source of monocytes that accumulate in injured tissues. Whether splenic monocytes contribute to monocyte alterations after CBDL is unknown. This study evaluates monocyte distributions and assesses effects of splenectomy on monocyte levels and pulmonary vascular and hepatic abnormalities in experimental HPS.
  
  
  METHODS
  Splenectomy was performed in CBDL animals. Monocyte levels in different tissues and circulation were assessed with CD68. Pulmonary alterations of HPS were evaluated with vascular endothelial growth factor-A (VEGF-A) levels, angiogenesis, and alveolar-arterial oxygen gradient (AaPO2). Liver abnormalities were evaluated with fibrosis (Sirius red), bile duct proliferation (CK-19), and enzymatic changes.
  
  
  RESULTS
  Monocyte levels increased in the lung and liver after CBDL and were accompanied by elevated circulating monocyte numbers. Splenectomy significantly decreased monocyte accumulation, VEGF-A levels, and angiogenesis in CBDL animal lung and improved AaPO2levels. In contrast, hepatic monocyte levels, fibrosis, and functional abnormalities were further exacerbated by spleen removal.
  
  
  CONCLUSIONS
  Splenic reservoir monocytes are a major source for lung monocyte accumulation after CBDL, and spleen removal attenuates the development of experimental HPS. Liver monocytes may have different origins, and accumulation is exacerbated after depletion of splenic reservoir monocytes. Tissue specific monocyte alterations, influenced by the spleen reservoir, have a significant impact on pulmonary complications of liver disease.
authors.affiliation: Department of Geriatric Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.|Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Junlan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Wenli
authors.initials: W
authors.lastname: Yang
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Bingqian
authors.initials: B
authors.lastname: Hu
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Fallon
mesh_terms: D000818:Animals; D002245:Carbon Dioxide / Q000097:blood; D003135:Common Bile Duct / Q000601:surgery; D020065:Hepatopulmonary Syndrome / Q000473:pathology*; D008099:Liver / Q000473:pathology; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008297:Male; D009000:Monocytes / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000473:pathology*; D013156:Splenectomy; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D002245:Carbon Dioxide; D010100:Oxygen
keywords: cell and molecular biology; common bile duct ligation; hepatopulmonary syndrome; monocyte; spleen