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Mechanism for phosphatidylserine-dependent erythrophagocytosis in mouse liver.
MedLine Citation:
PMID:  21427291     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Aged or damaged RBCs are effectively removed from the blood circulation by Kupffer cells in the liver, but little is known regarding the mechanism of the clearance process. Here we show that stabilin-1 and stabilin-2 in hepatic sinusoidal endothelial cells (HSECs) are critical in effectively clearing damaged RBCs in mouse liver. Damaged RBCs and phosphatidylserine (PS)-coated beads were effectively sequestered in the hepatic sinusoid regardless of the presence of Kupffer cells, suggesting a role for HSECs in PS-dependent sequestration of PS-exposed RBCs in the liver. HSECs mediate tethering of damaged RBCs in a PS-dependent manner via stabilin-1 and stabilin-2. In a sinusoid-mimicked co-culture system consisting of macrophages layered over HSECs, there was significant enhancement of the phagocytic capacity of macrophages, and this was mediated by stabilin-1 and stabilin-2 in HSECs. Liver-specific knockdown of stabilin-1 and stabilin-2 inhibited the sequestration of damaged RBCs in the hepatic sinusoid and delayed the elimination of damaged cells in an in vivo animal model. Thus, the roles of stabilin-1 and staiblin-2 in hepatic sequestration of PS-exposed RBCs may represent a potential mechanism for the clearance of damaged RBCs by Kupffer cells and for the control of some pathologic conditions such as hemolytic anemia.
Authors:
Sung-Jin Lee; Seung-Yoon Park; Mi-Yeon Jung; Sang Mun Bae; In-San Kim
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-22
Journal Detail:
Title:  Blood     Volume:  -     ISSN:  1528-0020     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea, Republic of;
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