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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2002-04-1080. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-04-1080v1 100/12/4026    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 Nassar, T. Articles by Higazi, A. A.-R. Search for Related Content PubMed PubMed Citation Articles by Nassar, T. Articles by Higazi, A. A.-R. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 December 2002, Vol. 100, No. 12, pp. 4026-4032 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Human -defensin regulates smooth muscle cell contraction: a role for low-density lipoprotein receptor-related protein/2-macroglobulin receptor Taher Nassar, Sa'ed Akkawi, Rachel Bar-Shavit, Abdullah Haj-Yehia, Khalil Bdeir, Abu-Bakr Al-Mehdi, Mark Tarshis, and Abd Al-Roof Higazi From the Departments of Clinical Biochemistry, Oncology, Interdepartmental Unit, and School of Pharmacy, Hadassah University Hospital and Hebrew University-Hadassah Medical School, Jerusalem, Israel; and the Department of Pathology and Laboratory Medicine and Department of Environmental Medicine, University of Pennsylvania, Philadelphia. We have previously identified -defensin in association with medial smooth muscle cells (SMCs) in human coronary arteries. In the present paper we report that -defensin, at concentrations below those found in pathological conditions, inhibits phenylephrine (PE)-induced contraction of rat aortic rings. Addition of 1 µM -defensin increased the half-maximal effective concentration (EC50) of PE on denuded aortic rings from 32 to 630 nM. The effect of -defensin was dose dependent and saturable, with a half-maximal effect at 1 µM. -Defensin binds to human umbilical vein SMCs in a specific manner. The presence of 1 µM -defensin inhibited the PE-mediated Ca++ mobilization in SMCs by more than 80%. The inhibitory effect of -defensin on contraction of aortic rings and Ca++ mobilization was completely abolished by anti-low-density lipoprotein receptor-related protein/2-macroglobulin receptor (LRP) antibodies as well as by the antagonist receptor-associated protein (RAP). -Defensin binds directly to isolated LRP in a specific and dose-dependent manner; the binding was inhibited by RAP as well as by anti-LRP antibodies. -Defensin is internalized by SMCs and interacts with 2 intracellular subtypes of protein kinase C (PKC) involved in muscle contraction,  and . RAP and anti-LRP antibodies inhibited the binding and internalization of -defensin by SMCs and its interaction with intracellular PKCs. These observations suggest that binding of -defensin to LRP expressed in SMCs leads to its internalization; internalized -defensin binds to PKC and inhibits its enzymatic activity, leading to decreased Ca++ mobilization and SMC contraction in response to PE. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Syeda, E. Tullis, A. S. Slutsky, and H. Zhang Human neutrophil peptides upregulate expression of COX-2 and endothelin-1 by inducing oxidative stress Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2769 - H2774. [Abstract] [Full Text] [PDF] M. Saraheimo, C. Forsblom, K. Pettersson-Fernholm, A. Flyvbjerg, P.-H. Groop, J. Frystyk, and on behalf of the FinnDiane Study Group Increased levels of {alpha}-defensin (-1, -2 and -3) in type 1 diabetic patients with nephropathy Nephrol. Dial. Transplant., March 1, 2008; 23(3): 914 - 918. 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