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Blood, 1 November 2008, Vol. 112, No. 9, pp. 3661-3670. Prepublished online as a Blood First Edition Paper on August 18, 2008; DOI 10.1182/blood-2008-03-142760. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2008-03-142760v1 112/9/3661    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Shi, C.-S. Articles by Wu, H.-L. Search for Related Content PubMed PubMed Citation Articles by Shi, C.-S. Articles by Wu, H.-L. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Lectin-like domain of thrombomodulin binds to its specific ligand Lewis Y antigen and neutralizes lipopolysaccharide-induced inflammatory response Chung-Sheng Shi1,2, Guey-Yueh Shi1,2, Shi-Ming Hsiao1,2, Yuan-Chung Kao1,2, Kuan-Lin Kuo1,2, Chih-Yuan Ma1,2, Cheng-Hsiang Kuo1,2, Bi-Ing Chang1,2, Chuan-Fa Chang3,4, Chun-Hung Lin3,4, Chi-Huey Wong3,4, and Hua-Lin Wu1,2 1 Department of Biochemistry and Molecular Biology, College of Medicine, and 2 Cardiovascular Research Center, National Cheng Kung University, Taiwan; and 3 Genomics Research Center and 4 Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan, Republic of China Thrombomodulin (TM), a widely expressing glycoprotein originally identified in vascular endothelium, is an important cofactor in the protein C anticoagulant system. TM appears to exhibit anti-inflammatory ability through both protein C–dependent and –independent pathways. We presently have demonstrated that recombinant N-terminal lectinlike domain of TM (rTMD1) functions as a protective agent against sepsis caused by Gram-negative bacterial infections. rTMD1 caused agglutination of Escherichia coli and Klebsiella pneumoniae and enhanced the macrophage phagocytosis of these Gram-negative bacteria. Moreover, rTMD1 bound to the Klebsiella pneumoniae and lipopolysaccharide (LPS) by specifically interacting with Lewis Y antigen. rTMD1 inhibited LPS-induced inflammatory mediator production via interference with CD14 and LPS binding. Furthermore, rTMD1 modulated LPS-induced mitogen-activated protein kinase and nuclear factor-B signaling pathway activations and inducible nitric oxide synthase expression in macrophages. Administration of rTMD1 protected the host by suppressing inflammatory responses induced by LPS and Gram-negative bacteria, and enhanced LPS and bacterial clearance in sepsis. Thus, rTMD1 can be used to defend against bacterial infection and inhibit LPS-induced inflammatory responses, suggesting that rTMD1 may be valuable in the treatment of severe inflammation in sepsis, especially in Gram-negative bacterial infections. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Delvaeye and E. M. Conway Coagulation and innate immune responses: can we view them separately? Blood, September 17, 2009; 114(12): 2367 - 2374. [Abstract] [Full Text] [PDF]

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