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Prepublished online as a Blood First Edition Paper on January 2, 2003December 27, 2002; DOI 10.1182/blood-2001-12-0289. This Article 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 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 Social Bookmarking                   What's this? Submitted December 19, 2001 Accepted November 25, 2002 Novel epinephrine and cyclic AMP-mediated activation of BCAM/Lu-dependent sickle (SS) RBC adhesion Patrick C Hines, Qin Zen, Sharran N Burney, Deborah Shea, Kenneth I Ataga, Eugene P Orringer, Marilyn J Telen, and Leslie V Parise* Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Department of Hematology, Duke University, Durham, NC, USA * Corresponding author; email: parise{at}med.unc.edu. The vaso-occlusive crisis is the major clinical feature of sickle cell anemia, which is believed to be initiated or sustained by sickle (SS) 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 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 over four-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, 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Johnson and M. J. Telen Adhesion molecules and hydroxyurea in the pathophysiology of sickle cell disease Haematologica, April 1, 2008; 93(4): 481 - 485. [Full Text] [PDF] M.-H. Odievre, V. Bony, M. Benkerrou, C. Lapoumeroulie, C. Alberti, R. Ducrocq, E. Jacqz-Aigrain, J. Elion, and J.-P. Cartron Modulation of erythroid adhesion receptor expression by hydroxyurea in children with sickle cell disease Haematologica, April 1, 2008; 93(4): 502 - 510. [Abstract] [Full Text] [PDF] T. J. Mankelow, N. Burton, F. O. Stefansdottir, F. A. Spring, S. F. Parsons, J. S. 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