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Prepublished online as a Blood First Edition Paper on January 2, 2003; DOI 10.1182/blood-2001-12-0289. This Article Full Text Full Text (PDF) All Versions of this Article: 2001-12-0289v1 2001-12-0289v2 101/8/3281    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 Hines, P. C. Articles by Parise, L. V. Search for Related Content PubMed PubMed Citation Articles by Hines, P. C. Articles by Parise, L. V. Related Collections Red Cells Cell Adhesion and Motility Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 April 2003, Vol. 101, No. 8, pp. 3281-3287 RED CELLS Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-dependent sickle (SS) RBC adhesion Patrick C. Hines, Qin Zen, Sharran N. Burney, Deborah A. Shea, Kenneth I. Ataga, Eugene P. Orringer, Marilyn J. Telen, and Leslie V. Parise From the Departments of Pharmacology and Medicine, Center for Thrombosis and Hemostasis, University of North Carolina at Chapel Hill (UNC-CH); Department of Hematology, Duke University, Durham, NC The vasoocclusive crisis is the major clinical feature of sickle cell anemia, which is believed to be initiated or sustained by sickle (SS) red blood cell (RBC) adhesion to the vascular wall. SS RBCs, but not unaffected (AA) RBCs, adhere avidly to multiple components of the vascular wall, including laminin. Here we report a novel role for epinephrine and cyclic adenosine monophosphate (cAMP) in the regulation of human SS RBC adhesiveness via the laminin receptor, basal cell adhesion molecule/Lutheran (BCAM/Lu). Our data demonstrate that peripheral SS RBCs contain greater than 4-fold more cAMP than AA RBCs under basal conditions. Forskolin or the stress mediator epinephrine further elevates cAMP in SS RBCs and increases adhesion of SS RBCs to laminin in a protein kinase A (PKA)-dependent manner, with the low-density population being the most responsive. Epinephrine-stimulated adhesion to laminin, mediated primarily via the 2-adrenergic receptor, occurred in SS RBC samples from 46% of patients and was blocked by recombinant, soluble BCAM/Lu, implicating this receptor as a target of cAMP signaling. Thus, these studies demonstrate a novel, rapid regulation of SS RBC adhesion by a cAMP-dependent pathway and suggest that components of this pathway, particularly PKA, the 2-adrenergic receptor, and BCAM/Lu, should be further explored as potential therapeutic targets to inhibit SS RBC adhesion. © 2003 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: C. Lanaro, C. F. Franco-Penteado, D. M. Albuqueque, S. T. O. Saad, N. Conran, and F. F. Costa Altered levels of cytokines and inflammatory mediators in plasma and leukocytes of sickle cell anemia patients and effects of hydroxyurea therapy J. Leukoc. Biol., February 1, 2009; 85(2): 235 - 242. [Abstract] [Full Text] [PDF] X. An, E. Gauthier, X. Zhang, X. Guo, D. J. Anstee, N. Mohandas, and J. A. 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