Role of splenic reservoir monocytes in pulmonary vascular monocyte accumulation in experimental hepatopulmonary syndrome

Abstract

Background and AimPulmonary 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.MethodsSplenectomy 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.ResultsMonocyte 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 AaPO2 levels. In contrast, hepatic monocyte levels, fibrosis, and functional abnormalities were further exacerbated by spleen removal.ConclusionsSplenic 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.

Intervention of Inflammatory Monocyte Activity Limits Dermal Fibrosis

“…Our results suggest that skin-infiltrating monocytes in scleroderma are recruited from the entire periphery and not, as previously suggested (Egawa et al, 2013), exclusively from the bone marrow. We could show that cells in dermal lesions are recruited from the splenic reservoir, as has also been shown for acute tissue damage (Wu et al, 2016).…”

Potential Clinical Targets in Hepatopulmonary Syndrome: Lessons From Experimental Models

“…Recruited monocytes are generally considered to be derived from progenitor cells in the bone marrow that migrate to the site of injury. However, a recent study found that splenic reservoir monocytes contribute to pulmonary monocyte accumulation in experimental HPS . Splenectomy decreased pulmonary monocyte influx and improved gas exchange but increased hepatic monocyte levels and significantly worsened liver function …”

“…However, a recent study found that splenic reservoir monocytes contribute to pulmonary monocyte accumulation in experimental HPS. (30) Splenectomy decreased pulmonary monocyte influx and improved gas exchange but increased hepatic monocyte levels and significantly worsened liver function. (30) One trigger for pulmonary intravascular monocyte accumulation appears to be bacterial translocation from the gut into the portal circulation.…”

“…(30) Splenectomy decreased pulmonary monocyte influx and improved gas exchange but increased hepatic monocyte levels and significantly worsened liver function. (30) One trigger for pulmonary intravascular monocyte accumulation appears to be bacterial translocation from the gut into the portal circulation. In the setting of cirrhosis, including CBDL, intestinal bacterial overgrowth, disruption of the gut mucosal barrier, decreased clearance capacity of the liver, and the development of portosystemic shunts allow circulating endotoxins to enter the pulmonary circulation.…”

Liver-protecting effects of extracts from Glossy privet fruit and Ecliptae herba formula in mice through suppression of Kupffer cells activation

“…Pieces of liver tissues were fixed in 4% formaldehyde for 24 h. Paraffin sections (5μm) were prepared and subjected to haematoxylin and eosin staining for general morphological observations. Masson Trichrome staining was performed according to Wu's report (Wu, Zhang, Yang, Hu, & Fallon, 2016). The images were captured using a light microscope (Nikon Eclipse TE2000-U, NIKON, Japan) and then photographed at 200× magnification.…”