| The conserved histidine in epidermal growth factor-like domains of stabilin-2 modulates pH-dependent recognition of phosphatidylserine in apoptotic cells. | |
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MedLine Citation:
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PMID: 20382256 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Soyoun Kim; Dong-Jun Bae; Mina Hong; Seung-Yoon Park; In-San Kim |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-09 |
Journal Detail:
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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:
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Created Date: 2010-06-02 Completed Date: 2010-09-27 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9508482 Medline TA: Int J Biochem Cell Biol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1154-63 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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0/Cell Adhesion Molecules, Neuronal; 0/Phosphatidylserines; 62229-50-9/Epidermal Growth Factor; 71-00-1/Histidine; 7440-70-2/Calcium |
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