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Blood, 15 January 2008, Vol. 111, No. 2, pp. 905-914. Prepublished online as a Blood First Edition Paper on October 2, 2007; DOI 10.1182/blood-2007-07-099465. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-07-099465v1 111/2/905    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 Setty, B. N. Y. Articles by Betal, S. G. Search for Related Content PubMed PubMed Citation Articles by Setty, B. N. Y. Articles by Betal, S. G. Related Collections Hemostasis, Thrombosis, and Vascular Biology Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Microvascular endothelial cells express a phosphatidylserine receptor: a functionally active receptor for phosphatidylserine-positive erythrocytes B. N. Yamaja Setty1, and Suhita Gayen Betal1 1 Marian Anderson Comprehensive Sickle Cell Anemia Care and Research Center, Department of Pediatrics, Division of Research Hematology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA Phosphatidylserine (PS)–positive erythrocytes adhere to endothelium and subendothelial matrix components. While thrombospondin mediates these inter-actions, it is unknown whether PS-associated erythrocyte-endothelial adhesion occurs in the absence of plasma ligands. Using ionophore-treated PS-expressing control HbAA erythrocytes, we demonstrate that PS-positive erythrocytes adhered to human lung microendothelial cells in the absence of plasma ligands, that this adhesion was enhanced following endothelial activation with IL-1, TNF-, LPS, hypoxia, and heme, and that this adhesive interaction was selective to erythrocyte PS. We next explored whether microendothelial cells express an adhesion receptor that recognizes cell surface–expressed PS (PSR) similar to that expressed on activated macrophages. We demonstrate constitutive expression of both PSR mRNA and protein that were up-regulated in a time-dependent manner following endothelial activation. While minimal PSR expression was noted on unstimulated cells, endothelial activation up-regulated PSR surface expression. In antibody-blocking studies, using PS-positive erythrocytes generated either artificially via ionophore treatment of control erythrocytes or from patients with sickle cell disease, we demonstrate that PSR was functional, supporting PS-mediated erythrocyte adhesion to activated endothelium. Our results demonstrate the existence of a novel functional adhesion receptor for PS on the microendothelium that is up-regulated by such pathologically relevant agonists as hypoxia, cytokines, and heme. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Faille, V. Combes, A. J. Mitchell, A. Fontaine, I. Juhan-Vague, M.-C. Alessi, G. Chimini, T. Fusai, and G. E. Grau Platelet microparticles: a new player in malaria parasite cytoadherence to human brain endothelium FASEB J, October 1, 2009; 23(10): 3449 - 3458. [Abstract] [Full Text] [PDF] G. J. Kato and M. T. Gladwin Evolution of Novel Small-Molecule Therapeutics Targeting Sickle Cell Vasculopathy JAMA, December 10, 2008; 300(22): 2638 - 2646. [Abstract] [Full Text] [PDF]

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