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Blood, 1 January 2009, Vol. 113, No. 1, pp. 165-174. Prepublished online as a Blood First Edition Paper on October 15, 2008; DOI 10.1182/blood-2008-05-158048. This Article Full Text (PDF) Supplemental Methods, Table, and Figures All Versions of this Article: blood-2008-05-158048v1 113/1/165    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Liao, D. Articles by Chen, C. Search for Related Content PubMed PubMed Citation Articles by Liao, D. Articles by Chen, C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 20, 2008 Accepted September 19, 2008 Human protein S inhibits the uptake of AcLDL and expression of SR-A through Mer receptor tyrosine kinase in human macrophages Dan Liao, Xinwen Wang, Min Li, Peter H. Lin, Qizhi Yao, and Changyi Chen* Molecular Surgeon Research Center, Division of Vascular Surgery and Endovascular Therapy, Baylor College of Medicine and Michael E. DeBakey VA Medical Center, Houston, TX, United States * Corresponding author; email: jchen{at}bcm.tmc.edu. Human protein S is an anticoagulation protein, which also has non-anticoagulant functions such as stimulating macrophage phagocytosis of apoptotic cells. However, it is unknown whether protein S could regulate the expression and function of macrophage scavenger receptor A (SR-A) in macrophages. Human THP-1 monocytes and peripheral blood monocytes were differentiated into macrophages and then treated with physiological concentrations of human protein S. We found that protein S significantly reduced acetylated LDL uptake and binding by macrophages and decreased the intracellular cholesteryl ester content. Protein S suppressed the expression of the SR-A at both mRNA and protein levels. Protein S reduced the SR-A promoter activity primarily through inhibition in the binding of transcription factors to the AP-1 promoter element in macrophages. Furthermore, human protein S could bind and induce phosphorylation of Mer receptor tyrosine kinase. Soluble Mer protein or tyrosine kinase inhibitor herbimycin A effectively blocked the effects of protein S on AcLDL uptake. Immunohistochemical analysis revealed that the level of protein S was substantially increased in human atherosclerotic arteries. Thus, human protein S can inhibit the expression and activity of SR-A through Mer RTK in macrophages, suggesting that human protein S is a modulator for macrophage functions in uptaking of modified lipoproteins. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Anwar, A. K. Keating, D. Joung, S. Sather, G. K. Kim, K. K. Sawczyn, L. Brandao, P. M. Henson, and D. K. Graham Mer tyrosine kinase (MerTK) promotes macrophage survival following exposure to oxidative stress J. Leukoc. Biol., July 1, 2009; 86(1): 73 - 79. [Abstract] [Full Text] [PDF]

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