This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Laudes, I. J. Articles by Ward, P. A. Search for Related Content PubMed PubMed Citation Articles by Laudes, I. J. Articles by Ward, P. A.

(American Journal of Pathology. 2002;160:1867-1875.)
© 2002 American Society for Investigative Pathology

Regular Articles

Anti-C5a Ameliorates Coagulation/Fibrinolytic Protein Changes in a Rat Model of Sepsis

Ines J. Laudes^*, Jeffrey C. Chu^*, Sujata Sikranth, Markus Huber-Lang^*, Ren-Feng Guo^*, Niels Riedemann^*, J. Vidya Sarma^*, Alvin H. Schmaier^* and Peter A. Ward^*

From the Departments of Pathology^*and Internal Medicine,University of Michigan Medical School, Ann Arbor, Michigan

Sepsis and trauma are the two most common causes of disseminated intravascular coagulation and multiple organ dysfunction syndrome. Both disseminated intravascular coagulation and the systemic inflammatory response syndrome often lead to multiple organ dysfunction syndrome. The current studies have evaluated the relationship between the anaphylatoxin, C5a, and changes in the coagulation/fibrinolytic systems during the cecal ligation and puncture (CLP) model of sepsis in rats. CLP animals treated with anti-C5a had a much improved number of survivors (63%) compared to rats treated with pre-immune IgG (31%). In CLP rats treated with pre-immune IgG there was clearly increased procoagulant activity with prolongation of the activated partial thromboplastin time and prothrombin time, reduced platelet counts, and increased levels of plasma fibrinogen. Evidence for thrombin formation was indicated by early consumption of factor VII:C, subsequent consumption of factors XI:C and IX:C and anti-thrombin and increased levels of the thrombin-anti-thrombin complex and D-dimer. Limited activation of fibrinolysis was indicated by reduced plasma levels of plasminogen and increased levels of tissue plasminogen activator and plasminogen activator inhibitor. Most of these parameters were reversed in CLP rats that had been treated with anti-C5a. Production of C5a during sepsis may directly or indirectly cause hemostatic defects that can be reduced by blockade of C5a.

This article has been cited by other articles:

				M. A. Flierl, D. Rittirsch, B. A. Nadeau, D. E. Day, F. S. Zetoune, J. V. Sarma, M. S. Huber-Lang, and P. A. Ward Functions of the complement components C3 and C5 during sepsis FASEB J, October 1, 2008; 22(10): 3483 - 3490. [Abstract] [Full Text] [PDF]

				P. A. Ward Role of the complement in experimental sepsis J. Leukoc. Biol., March 1, 2008; 83(3): 467 - 470. [Abstract] [Full Text] [PDF]

				K. Ritis, M. Doumas, D. Mastellos, A. Micheli, S. Giaglis, P. Magotti, S. Rafail, G. Kartalis, P. Sideras, and J. D. Lambris A Novel C5a Receptor-Tissue Factor Cross-Talk in Neutrophils Links Innate Immunity to Coagulation Pathways J. Immunol., October 1, 2006; 177(7): 4794 - 4802. [Abstract] [Full Text] [PDF]

				T. Sprong, D. Roos, C. Weemaes, C. Neeleman, C. L. M. Geesing, T. E. Mollnes, and M. van Deuren Deficient alternative complement pathway activation due to factor D deficiency by 2 novel mutations in the complement factor D gene in a family with meningococcal infections Blood, June 15, 2006; 107(12): 4865 - 4870. [Abstract] [Full Text] [PDF]

				A. D. Niederbichler, L. M. Hoesel, M. V. Westfall, H. Gao, K. R. Ipaktchi, L. Sun, F. S. Zetoune, G. L. Su, S. Arbabi, J. V. Sarma, et al. An essential role for complement C5a in the pathogenesis of septic cardiac dysfunction J. Exp. Med., January 23, 2006; 203(1): 53 - 61. [Abstract] [Full Text] [PDF]

				N. C. Riedemann, R.-F. Guo, and P. A. Ward A key role of C5a/C5aR activation for the development of sepsis J. Leukoc. Biol., December 1, 2003; 74(6): 966 - 970. [Abstract] [Full Text]

				T. Sprong, P. Brandtzaeg, M. Fung, A. M. Pharo, E. A. Hoiby, T. E. Michaelsen, A. Aase, J. W. M. van der Meer, M. van Deuren, and T. E. Mollnes Inhibition of C5a-induced inflammation with preserved C5b-9-mediated bactericidal activity in a human whole blood model of meningococcal sepsis Blood, November 15, 2003; 102(10): 3702 - 3710. [Abstract] [Full Text] [PDF]

				W. C. Aird The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome Blood, May 15, 2003; 101(10): 3765 - 3777. [Abstract] [Full Text] [PDF]

				I. J. Laudes, J. C. Chu, M. Huber-Lang, R.-F. Guo, N. C. Riedemann, J. V. Sarma, F. Mahdi, H. S. Murphy, C. Speyer, K. T. Lu, et al. Expression and Function of C5a Receptor in Mouse Microvascular Endothelial Cells J. Immunol., November 15, 2002; 169(10): 5962 - 5970. [Abstract] [Full Text] [PDF]