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Blood, 1 March 2005, Vol. 105, No. 5, pp. 2141-2145. Prepublished online as a Blood First Edition Paper on November 18, 2004; DOI 10.1182/blood-2004-04-1578. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1578v1 105/5/2141    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 Willekens, F. L. A. Articles by van Berkel, T. J. C. Search for Related Content PubMed PubMed Citation Articles by Willekens, F. L. A. Articles by van Berkel, T. J. C. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Liver Kupffer cells rapidly remove red blood cell–derived vesicles from the circulation by scavenger receptors Frans L. A. Willekens, Jan M. Werre, J. Kar Kruijt, Bregt Roerdinkholder-Stoelwinder, Yvonne A. M. Groenen-Döpp, Annegeet G. van den Bos, Giel J. C. G. M. Bosman, and Theo J. C. van Berkel From the Department of Clinical Chemistry, Rijnstate Hospital, Arnhem; Department of Blood Transfusion and Transplantation Immunology and Department of Biochemistry, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen; and Division of Biopharmaceutics, Leiden University, Leiden, The Netherlands. Previous studies have shown that during the lifespan of red blood cells (RBCs) 20% of hemoglobin is lost by shedding of hemoglobin-containing vesicles. However, the fate of these vesicles is unknown. To study this fate we used a rat model, after having established that rat RBCs lose hemoglobin in the same way as human RBCs, and that RBC-derived vesicles are preferentially labeled by CrO4. Such labeled vesicles were injected into recipient rats. Within 5 minutes, 80% of the radioactivity was cleared from the circulation with a concomitant uptake by the liver of 55% of the injected dose. After 30 minutes, Kupffer cells contained considerable amounts of hemoglobin and were shown to be responsible for 92% of the liver uptake. Vesicle clearance from the blood as well as liver uptake were significantly inhibited by preinjection of the scavenger-receptor ligands polyinosinic acid and phosphatidylserine. We conclude that in rats Kupffer cells rapidly remove RBC-derived vesicles from the circulation, mainly by scavenger receptors. The same mechanism is likely to be responsible for the elimination of human RBC vesicles, thereby constituting an important pathway for the breakdown of RBCs in humans. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. C. Saunderson, P. C. Schuberth, A. C. Dunn, L. Miller, B. D. Hock, P. A. MacKay, N. Koch, R. W. Jack, and A. D. McLellan Induction of Exosome Release in Primary B Cells Stimulated via CD40 and the IL-4 Receptor J. Immunol., June 15, 2008; 180(12): 8146 - 8152. [Abstract] [Full Text] [PDF] D. Periard, C. M. Boulanger, S. Eyer, N. Amabile, P. Pugin, C. Gerschheimer, and D. Hayoz Are Circulating Endothelial-Derived and Platelet-Derived Microparticles a Pathogenic Factor in the Cisplatin-Induced Stroke? Stroke, May 1, 2007; 38(5): 1636 - 1638. [Abstract] [Full Text] [PDF] C. M. Boulanger, N. Amabile, and A. Tedgui Circulating Microparticles: A Potential Prognostic Marker for Atherosclerotic Vascular Disease Hypertension, August 1, 2006; 48(2): 180 - 186. [Full Text] [PDF]

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