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Blood, 12 November 2009, Vol. 114, No. 20, pp. 4538-4545. Prepublished online as a Blood First Edition Paper on August 24, 2009; DOI 10.1182/blood-2009-03-205096. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-03-205096v1 114/20/4538    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 Google Scholar Articles by Licht, C. Articles by Kahr, W. H. A. PubMed PubMed Citation Articles by Licht, C. Articles by Kahr, W. H. A. Related Collections Platelets and Thrombopoiesis Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLATELETS AND THROMBOPOIESIS Platelet-associated complement factor H in healthy persons and patients with atypical HUS Christoph Licht1,2, Fred G. Pluthero2, Ling Li2, Hilary Christensen3, Sandra Habbig4, Bernd Hoppe4, Denis F. Geary1, Peter F. Zipfel5,6, and Walter H. A. Kahr2,3 1 Department of Paediatrics, Division of Nephrology, The Hospital for Sick Children, and University of Toronto, Toronto, ON; 2 Program in Cell Biology, Research Institute of The Hospital for Sick Children, Toronto, ON; and 3 Department of Paediatrics, Division of Haematology/Oncology, The Hospital for Sick Children, and University of Toronto, Toronto, ON; 4 Division of Paediatric Nephrology, Children's Hospital of the University of Cologne, Cologne, Germany; and 5 Leibniz Institute for Natural Products Research and Infection Biology and 6 Friedrich-Schiller-University, Jena, Germany Atypical hemolytic uremic syndrome (aHUS) is associated with complement system dysregulation, and more than 25% of pediatric aHUS cases are linked to mutations in complement factor H (CFH) or CFH autoantibodies. The observation of thrombocytopenia and platelet-rich thrombi in the glomerular microvasculature indicates that platelets are intimately involved in aHUS pathogenesis. It has been reported that a releasable pool of platelet CFH originates from -granules. We observed that platelet CFH can arise from endogenous synthesis in megakaryocytes and that platelets constitutively lacking -granules contain CFH. Electron and high-resolution laser fluorescence confocal microscopy revealed that CFH was present throughout the cytoplasm and on the surface of normal resting platelets with no evident concentration in -granules, lysosomes, or dense granules. Therapeutic plasma transfusion in a CFH-null aHUS patient revealed that circulating platelets take up CFH with similar persistence of CFH in platelets and plasma in vivo. Washed normal platelets were also observed to take up labeled CFH in vitro. Exposure of washed normal platelets to plasma of an aHUS patient with CFH autoantibodies produced partial platelet aggregation or agglutination, which was prevented by preincubation of platelets with purified CFH. This CFH-dependent response did not involve P-selectin mobilization, indicating a complement-induced platelet response distinct from -granule secretion. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Platelet CFH: in search of the source Jan Willem N. Akkerman Blood 2009 114: 4323-4324. [Full Text] [PDF] This article has been cited by other articles: J. W. N. Akkerman Platelet CFH: in search of the source Blood, November 12, 2009; 114(20): 4323 - 4324. [Full Text] [PDF]

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