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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2455-2462. Prepublished online as a Blood First Edition Paper on June 13, 2006; DOI 10.1182/blood-2006-04-017251. This Article Full Text (PDF) All Versions of this Article: blood-2006-04-017251v1 108/7/2455    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 Khan, S. Y. Articles by Silliman, C. C Search for Related Content PubMed PubMed Citation Articles by Khan, S. Y. Articles by Silliman, C. C Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 14, 2006 Accepted May 13, 2006 Soluble CD40 ligand accumulates in stored blood components, primes neutrophils through CD40, and is a potential cofactor in the development of transfusion-related acute lung injury Samina Yasmin Khan, Marguerite R Kelher, Joanna M Heal, Neil Blumberg, Lynn K Boshkov, Richard Phipps, Kelly F Gettings, Nathan J McLaughlin, and Christopher C Silliman* Department of Surgery, University of Colorado School of Medicine, Denver, CO Transfusion Med, Hematology-Oncology, Environmental Med, Immunology & Lung Biol., Pathology, Oregon Health Sciences University, Portland, OR Department of Pediatrics, University of Colorado School of Medicine, Denver, CO Bonfils Blood Center, Denver, CODepartment of Pediatrics, University of Colorado School of Medicine, * Corresponding author; email: christopher.silliman{at}uchsc.edu. TRALI is a post-transfusion acute pulmonary insufficiency, which has been linked to the infusion of biological response modifiers (BRMs) including anti-leukocyte antibodies and lipids. Soluble CD40 ligand (sCD40L) is a platelet-derived pro-inflammatory mediator that accumulates during platelet storage. We hypothesize that human PMNs express CD40, CD40 ligation rapidly primes PMNs, and sCD40L induces PMN- mediated cytotoxicity of human pulmonary microvascular endothelial cells (HMVECs). Levels of sCD40L were measured in blood components and in platelet concentrates (PCs) implicated in TRALI or control PCs that did not elicit a transfusion reaction. All blood components contained higher levels of sCD40L than fresh plasma with apheresis PCs evidencing the highest concentration of sCD40L followed by PCs from whole blood, whole blood, and PRBCs. PCs implicated in TRALI reactions contained significantly higher sCD40L levels as compared to control PCs. PMNs express functional CD40 on the plasma membrane and recombinant sCD40L [10 ng/ml-1 ; µg/ml] rapidly (5 min) primed the PMN oxidase. Soluble CD40L promoted PMN-mediated cytotoxicity of HMVECs as the second event in a two-event in vitro model of TRALI. We conclude that sCD40L, which accumulates during blood component storage, has the capacity to activate adherent PMNs causing endothelial damage and may cause TRALI in predisposed patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Hot on the trail of TRALI David F. Stroncek Blood 2006 108: 2136-2137. [Full Text] [PDF] This article has been cited by other articles: P. C. Eckels, A. Banerjee, E. E. Moore, N. J. D. McLaughlin, L. M. Gries, M. R. Kelher, K. M. England, F. Gamboni-Robertson, S. Y. Khan, and C. C. Silliman Amantadine inhibits platelet-activating factor induced clathrin-mediated endocytosis in human neutrophils Am J Physiol Cell Physiol, October 1, 2009; 297(4): C886 - C897. [Abstract] [Full Text] [PDF] R. P. Phipps and N. Blumberg Statin Islands and PPAR Ligands in Platelets Arterioscler Thromb Vasc Biol, May 1, 2009; 29(5): 620 - 621. [Full Text] [PDF] D. J. Triulzi Transfusion-Related Acute Lung Injury: Current Concepts for the Clinician Anesth. Analg., March 1, 2009; 108(3): 770 - 776. [Abstract] [Full Text] [PDF] M. R. Kelher, T. Masuno, E. E. Moore, S. Damle, X. Meng, Y. Song, X. Liang, J. Niedzinski, S. S. Geier, S. Y. Khan, et al. Plasma from stored packed red blood cells and MHC class I antibodies causes acute lung injury in a 2-event in vivo rat model Blood, February 26, 2009; 113(9): 2079 - 2087. [Abstract] [Full Text] [PDF] F. Cognasse, J. M. Payrat, L. Corash, J. C. Osselaer, and O. Garraud Platelet components associated with acute transfusion reactions: the role of platelet-derived soluble CD40 ligand Blood, December 1, 2008; 112(12): 4779 - 4780. [Full Text] [PDF] B. D. Elzey, S. A. Crist, D. L. Sprague, and T. L. Ratliff Response: Are PDMVs the biologically active source of CD154 in ATR? Blood, December 1, 2008; 112(12): 4780 - 4781. [Full Text] [PDF] R. S. Jawa, S. Anillo, and M. N. Kulaylat Transfusion-Related Acute Lung Injury J Intensive Care Med, March 1, 2008; 23(2): 109 - 121. [Abstract] [PDF] C. Beauvillain, Y. Delneste, M. Scotet, A. Peres, H. Gascan, P. Guermonprez, V. Barnaba, and P. Jeannin Neutrophils efficiently cross-prime naive T cells in vivo Blood, October 15, 2007; 110(8): 2965 - 2973. [Abstract] [Full Text] [PDF] J. M. Cholette, J. S. Rubenstein, G. M. Alfieris, M. P. McDermott, W. G. Harmon, R. Vermilion, M. P. Eaton, J. J. Gangemi, and N. B. Lerner Elevated Risk of Thrombosis in Neonates Undergoing Initial Palliative Cardiac Surgery Ann. Thorac. Surg., October 1, 2007; 84(4): 1320 - 1325. [Abstract] [Full Text] [PDF] C. C. Silliman, B. R. Curtis, P. M. Kopko, S. Y. Khan, M. R. Kelher, R. M. Schuller, B. Sannoh, and D. R. Ambruso Donor antibodies to HNA-3a implicated in TRALI reactions prime neutrophils and cause PMN-mediated damage to human pulmonary microvascular endothelial cells in a two-event in vitro model Blood, February 15, 2007; 109(4): 1752 - 1755. [Abstract] [Full Text] [PDF]

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