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Complement in Human Disease Clinical and Developmental Immunology Complement in Human Disease Guest Editors: Michael A. Flierl, Daniel Rittirsch, Markus S. Huber-Lang, and Philip F. Stahel Complement in Human Disease Clinical and Developmental Immunology Complement in Human Disease Guest Editors: Michael A. Flierl, Daniel Rittirsch, Markus S. Huber-Lang, and Philip F. Stahel Copyright © 2013 Hindawi Publishing Corporation. All rights reserved. This is a special issue published in “Clinical and Developmental Immunology.” All articles are open access articles distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editorial Board B. Dicky Akanmori, Ghana H. Inoko, Japan G. Opdenakker, Belgium R. Baughman, USA David Kaplan, USA Ira Pastan, USA Stuart Berzins, Australia W. Kast, USA Berent Prakken, The Netherlands Bengt Bjorksten, Sweden Taro Kawai, Japan Nima Rezaei, Iran K. Blaser, Switzerland Michael H. Kershaw, Australia Clelia M. Riera, Argentina Federico Bussolino, Italy Hiroshi Kiyono, Japan Luigina Romani, Italy Nitya G. Chakraborty, USA Shigeo Koido, Japan Aurelia Rughetti, Italy Robert B. Clark, USA Guido Kroemer, France Takami Sato, USA Mario Clerici, Italy H. Kim Lyerly, USA Senthamil R. Selvan, USA Edward P. Cohen, USA Enrico Maggi, Italy Naohiro Seo, Japan Robert E. Cone, USA Stuart Mannering, Australia E. M. Shevach, USA Nathalie Cools, Belgium Eiji Matsuura, Japan George B. Stefano, USA Mark J. Dobrzanski, USA C. J. M. Melief, The Netherlands Trina J. Stewart, Australia Nejat Egilmez, USA Jiri Mestecky, USA Helen Su, USA Eyad Elkord, UK C. Morimoto, Japan Jacek Tabarkiewicz, Poland Steven E. Finkelstein, USA Hiroshi Nakajima, Japan Ban-Hock Toh, Australia Richard L. Gallo, USA Tetsuya Nakatsura, Japan J. F. Urban, USA Luca Gattinoni, USA T. Nakayama, Japan Yvette Van Kooyk, The Netherlands David E. Gilham, UK H. W. Nijman, The Netherlands Xiao-Feng Yang, USA Ronald B. Herberman, USA Paola Nistico, Italy Y. Yoshikai, Japan D. Craig Hooper, USA Graham Ogg, UK Qiang Zhang, USA Contents Complement in Human Disease, Michael A. Flierl, Daniel Rittirsch, Markus S. Huber-Lang, and Philip F. Stahel Volume 2013, Article ID 920474, 2 pages Complement Activation and Inhibition in Wound Healing, Gwendolyn Cazander, Gerrolt N. Jukema, and Peter H. Nibbering Volume 2012, Article ID 534291, 14 pages Dual Functions of the C5a Receptor as a Connector for the K562 Erythroblast-Like Cell-THP-1 Macrophage-Like Cell Island and as a Sensor for the Differentiation of the K562 Erythroblast-Like Cell during Haemin-Induced Erythropoiesis, Hiroshi Nishiura, Rui Zhao, and Tetsuro Yamamoto Volume 2012, Article ID 187080, 12 pages Role of Complement in Multiorgan Failure, Daniel Rittirsch, Heinz Redl, and Markus Huber-Lang Volume 2012, Article ID 962927, 10 pages Complement Diagnostics: Concepts, Indications, and Practical Guidelines, Bo Nilsson and Kristina Nilsson Ekdahl Volume 2012, Article ID 962702, 11 pages Kidney Diseases Caused by Complement Dysregulation: Acquired, Inherited, and Still More to Come, Saskia F. Heeringa and Clemens D. Cohen Volume 2012, Article ID 695131, 6 pages The Effect of Weight Loss on Serum Mannose-Binding Lectin Levels,P.H.Høyem,J.M.Bruun, S. B. Pedersen, S. Thiel, B. Richelsen, J. S. Christiansen, and T. K. Hansen Volume 2012, Article ID 354894, 5 pages Familial Atypical Hemolytic Uremic Syndrome: A Review of Its Genetic and Clinical Aspects, Fengxiao Bu, Nicolo Borsa, Ardissino Gianluigi, and Richard J. H. Smith Volume 2012, Article ID 370426, 9 pages Initiation and Regulation of Complement during Hemolytic Transfusion Reactions,SeanR.Stowell, Anne M. Winkler, Cheryl L. Maier, C. Maridith Arthur, Nicole H. Smith, Kathryn R. Girard-Pierce, Richard D. Cummings, James C. Zimring, and Jeanne E. Hendrickson Volume 2012, Article ID 307093, 12 pages TheRoleofComplementSysteminSepticShock, Jean Charchaflieh, Jiandong Wei, Georges Labaze, Yunfang Joan Hou, Benjamin Babarsh, Helen Stutz, Haekyung Lee, Samrat Worah, and Ming Zhang Volume 2012, Article ID 407324, 8 pages Complement Factor C7 Contributes to Lung Immunopathology Caused by Mycobacterium tuberculosis, Kerry J. Welsh, Cole T. Lewis, Sydney Boyd, Michael C. Braun, and Jeffrey K. Actor Volume 2012, Article ID 429675, 7 pages Hindawi Publishing Corporation Clinical and Developmental Immunology Volume 2013, Article ID 920474, 2 pages http://dx.doi.org/10.1155/2013/920474 Editorial Complement in Human Disease Michael A. Flierl,1 Daniel Rittirsch,2 Markus S. Huber-Lang,3 and Philip F. Stahel4 1 Department of Orthopaedic Surgery, School of Medicine, University of Colorado, Aurora, CO 80045, USA 2 Division of Trauma Surgery, Department of Surgery, University Hospital Zurich, 8006 Zurich, Switzerland 3 Department of Trauma-, Hand-, and Reconstructive Surgery, University Hospital Ulm, 89081 Ulm, Germany 4 DepartmentofOrthopaedicSurgery,DenverHealthMedicalCenter,SchoolofMedicine,UniversityofColorado, Denver, CO 80204, USA Correspondence should be addressed to Michael A. Flierl, michael.�ierl�ucdenver.edu Received 9 January 2013; Accepted 9 January 2013 Copyright © 2013 Michael A. Flierl et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. As part of innate immunity, the complement system embod- and demonstrate how revesal of complement hyperactivity ies the “�rst line of defense” to various initial insults, includ- using several complement inhibitors has resulted in novel and ing trauma, infection, hemorrhage, ischemia, and autoim- innovative wound care strategies, which may soon be subject munity. While of bene�cial intention, excessive complement of clinical trials. activation can inadvertently damage healthy host tissues and K. J. Welsh et al. challenge recent evidence that com- thereby exacerbate the initial pathological events by causing plement plays a critical role in the host defense against an “innocent bystander effect.” Mycobacterium tuberculosis. Following aerosol challenge with “Complementology” represents a rapidly evolving �eld. Mycobacterium tuberculosis, the authors demonstrate that Recent scienti�c efforts have identi�ed novel complement “C7-knockout” mice had markedly reduced liver colony activation pathways and select complement-inhibiting com- forming units and lung occlusion in conjunction with signif- pounds, which have been shown to ameliorate myriad icantly increased total lymphocytes, decreased macrophages, autoimmune or in�ammatory conditions. ese �ndings and increased numbers of CD4+ cells. In line, expression have renewed the enthusiasm for novel pharmacologi- of lung IFN- and TNF- was increased in these animals, cal strategies targeting numerous in�ammatory conditions, underscoring a crucial role of C7 in the disease manifestation which currently elude successful transfer “from bench to of Mycobacterium tuberculosis . bedside,” such as acute lung injury, sepsis, burn, ischemia- S. R. Stowell et al.’s manuscript reviews the role of reperfusion injury, traumatic brain injury, and kidney dis- complement in transfusion-related mortality. is is of par- ease. ticular interest, as excessive complement activation during e abundant involvement of the complement system in transfusion represents one of the most common features humanhealthanddiseaseisre�ectedbythewiderangeof associated with fatality. e treating physician is furthermore topics covered in this special issue of Clinical and Develop- provided with several strategies aiming to immunomodulate mental Immunology. the complement system during incompatible red blood cell B. Nilsson and N. Ekdahl provide a summarizing article transfusions. on current indications, techniques, sampling, and interpre- In two reviews, F. Bu et al. and S. F. Heeringa and tations for clinical complement analyses. In addition, an colleagues review complement involvement in renal disease. easy-to-follow algorithm is provided for routine laboratory Bu reviews the pathogenetic role of genetic variations in operations. complement genes and complement dysregulation at the G. Cazander et al. illustrate the success of targeted cell surface results in different forms of atypical hemolytic complement inhibition of complement in wound healing uremic syndrome, and how this understanding may result in 2 Clinical and Developmental Immunology novel complement-modulating treatment approaches. In S. F. Heeringa’s paper, the pathogenesis of complement associated glomerulopathies is reviewed. Heeringa describes how defec- tive complement control via the alternative pathway results in glomerular C3 deposition and how this understanding has generated a complement pan-blockade or plasma substitu- tion as potential treatment strategies, which have been proven successful. H. Nishiura et al. shed further light on the importance of the C5a receptor (C5aR) during erythropoiesis. Strikingly, expression and regulation of RP S19 oligomer, which binds to C5aR, may regulate C5aR function as a connector for the erythroblast-macrophage island or for erythroblast differen- tiationinthebonemarrow. D. Rittirsch et al. and �. Charcha�ieh et al. review the highly elaborate immune response following trauma and sepsis, which is—at least in part—driven by excessive complement activation and may result in a deadly downward spiral of SIRS, sepsis, septic shock, and multiorgan failure. Recent clinical concepts,
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