Document Detail


The conserved histidine in epidermal growth factor-like domains of stabilin-2 modulates pH-dependent recognition of phosphatidylserine in apoptotic cells.
MedLine Citation:
PMID:  20382256     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Clearance of apoptotic cells is involved in the resolution of inflammation, and this mechanism is controlled by the regulation of pro- and anti-inflammatory cytokine production during the ingestion of apoptotic cells. Inflamed areas show extracellular acidity, and low pH stimulates cellular functions of immune cells. However, little is known about the influence of extracellular acidic pH on the function of phagocytic cells. In this study, we showed that stabilin-2-mediated phagocytosis is activated in low pH media (pH 6.8) and examined the molecular mechanisms underlying this pH-dependent enhancement of phagocytic activity. Stabilin-2, which is expressed in human monocyte derived macrophages (HMDM), is a phosphatidylserine (PS) receptor that mediates phagocytosis of apoptotic cells, and releases the anti-inflammatory cytokine, TGF-beta. The PS binding activity of stabilin-2 is enhanced in low pH, and a conserved histidine(1403) in close proximity to the PS binding loop is critical for pH-dependent activity. We propose that protonation of His(1403) may rearrange the PS binding loop to enhance binding affinity in low pH, indicating that acidic pH might act as a danger signal to stimulate stabilin-2-mediated phagocytosis to resolve inflammation. Considering that phosphatidylserine is an important target molecule for apoptotic cells in the acidic microenvironment of inflammation and tumors, our results also have implications for pH sensitive targeting of apoptotic cells.
Authors:
Soyoun Kim; Dong-Jun Bae; Mina Hong; Seung-Yoon Park; In-San Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-09
Journal Detail:
Title:  The international journal of biochemistry & cell biology     Volume:  42     ISSN:  1878-5875     ISO Abbreviation:  Int. J. Biochem. Cell Biol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-02     Completed Date:  2010-09-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9508482     Medline TA:  Int J Biochem Cell Biol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1154-63     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Apoptosis*
Calcium / metabolism
Cell Adhesion Molecules, Neuronal / chemistry*,  metabolism*
Conserved Sequence*
Epidermal Growth Factor / chemistry*
Erythrocytes / cytology,  metabolism
Female
Histidine / metabolism*
Humans
Hydrogen-Ion Concentration
L Cells (Cell Line)
Mice
Mice, Inbred BALB C
Models, Molecular
Molecular Sequence Data
Phagocytosis
Phosphatidylserines / metabolism*
Protein Binding
Protein Structure, Secondary
Protein Structure, Tertiary
Structural Homology, Protein
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Cell Adhesion Molecules, Neuronal; 0/Phosphatidylserines; 62229-50-9/Epidermal Growth Factor; 71-00-1/Histidine; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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