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Vol. 2, No. 1, 2010
Issue release date: December 2009
Free Access
J Innate Immun 2010;2:87–92
(DOI:10.1159/000247157)

Protective Role of Complement C5a in an Experimental Model of Staphylococcus aureus Bacteremia

von Köckritz-Blickwede M.a · Konrad S.b · Foster S.c · Gessner J.E.b · Medina E.a
aInfection Immunology Research Group, Helmholtz Center for Infection Research, Braunschweig, bClinic for Immunology and Rheumatology, Hanover Medical School, Hanover, Germany; cDepartment of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield, UK
email Corresponding Author

Abstract

The complement system is a key component of the innate immune response. Here, we have examined the role of complement anaphylatoxin C5a in an experimental model of Staphylococcus aureus bacteremia. Our data provide compelling evidence for a protective role of C5a during staphylococcal bloodstream infection.


 goto top of outline Key Words

  • Bacteremia
  • Complement C5a
  • Infection, susceptibility
  • Staphylococcus aureus

 goto top of outline Abstract

The complement system is a key component of the innate immune response. Here, we have examined the role of complement anaphylatoxin C5a in an experimental model of Staphylococcus aureus bacteremia. Our data provide compelling evidence for a protective role of C5a during staphylococcal bloodstream infection.

Copyright © 2009 S. Karger AG, Basel


 goto top of outline References
  1. Lowy FD: Antimicrobial resistance: the example of Staphylococcus aureus. J Clin Invest 2003;111:1265–1273.
  2. Boucher HW, Corey GR: Epidemiology of methicillin-resistant Staphylococcus aureus. Clin Infect Dis 2008;46(suppl 5):S344–S349.
  3. Frank MM, Fries LM: The role of complement in inflammation and phagocytosis. Immunol Today 1991;12:322–326.
  4. Guo RF, Ward PA: Role of C5a in inflammatory responses. Annu Rev Immunol 2005;23:821–852.
  5. Gasque P: Complement: a unique innate immune sensor for danger signals. Mol Immunol 2004;41:1089–1098.
  6. Cerquetti MC, Sordelli DO, Ortegon RA, Bellanti JA: Impaired lung defenses against Staphylococcus aureus in mice with hereditary deficiency of the fifth component of complement. Infect Immun 1983;41:1071–1076.
  7. Höpken UE, Lu B, Gerard NP, Gerard C: The C5a chemoattractant receptor mediates mucosal defence to infection. Nature 1996;383:86–89.
  8. Naber CK: Future strategies for treating Staphylococcus aureus bloodstream infections. Clin Microbiol Infect 2008;14(suppl 2):26–34.

    External Resources

  9. von Köckritz-Blickwede M, Rohde M, Oehmcke S, Miller LS, Cheung AL, Herwald H, Foster S, Medina E: Immunological mechanisms underlying the genetic predisposition to severe Staphylococcus aureus infection in the mouse model. Am J Pathol 2008;173:1657–1668.
  10. Nilsson UR, Müller-Eberhard HJ: Deficiency of the fifth component of complement in mice with an inherited complement defect. J Exp Med 1967;125:1–16.
  11. Jacobs JC, Miller ME: Fatal familial Leiner’s disease: a deficiency of the opsonic activity of serum complement. Pediatrics 1972;49:225–232.
  12. Delgado-Cerviño E, Fontán G, López-Trascasa M: C5 complement deficiency in a Spanish family: molecular characterization of the double mutation responsible for the defect. Mol Immunol 2005;42:105–111.

    External Resources

  13. Stevens JH, O’Hanley P, Shapiro JM, Mihm FG, Satoh PS, Collins JA, and Raffin TA: Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates. J Clin Invest 1986;77:1812–1816.
  14. Czermak BJ, Sarma V, Pierson CL, Warner RL, Huber-Lang M, Bless NM, Schmal H, Friedl HP, Ward PA: Protective effects of C5a blockade in sepsis. Nat Med 1999;5:788–792.
  15. Laudes IJ, Chu JC, Sikranth S, Huber-Lang M, Guo RF, Riedemann N, Sarma JV, Schmaier AH, Ward PA: Anti-C5a ameliorates coagulation/fibrinolytic protein changes in a rat model of sepsis. Am J Pathol 2002;160:1867–1875.
  16. Ward PA: Role of the complement in experimental sepsis. J Leukoc Biol 2008;83:467–470.
  17. Martin GS, Mannino DM, Eaton S, Moss M: The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003;348:1546–1554.

 goto top of outline Author Contacts

PD Dr. Eva Medina
Infection Immunology Research Group
Helmholtz Center for Infection Research
Inhoffenstrasse 7, DE–38124 Braunschweig (Germany)
Tel. +49 531 6181 4500, Fax +49 531 6181 4499, E-Mail eva.medina@helmholtz-hzi.de


 goto top of outline Article Information

Received: August 11, 2009
Accepted after revision: August 17, 2009
Published online: October 10, 2009
Number of Print Pages : 6
Number of Figures : 3, Number of Tables : 0, Number of References : 17
Additional supplementary material is available online - Number of Parts : 1


 goto top of outline Publication Details

Journal of Innate Immunity

Vol. 2, No. 1, Year 2010 (Cover Date: December 2009)

Journal Editor: Herwald H. (Lund), Egesten A. (Lund)
ISSN: 1662-811X (Print), eISSN: 1662-8128 (Online)

For additional information: http://www.karger.com/JIN


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

The complement system is a key component of the innate immune response. Here, we have examined the role of complement anaphylatoxin C5a in an experimental model of Staphylococcus aureus bacteremia. Our data provide compelling evidence for a protective role of C5a during staphylococcal bloodstream infection.



 goto top of outline Author Contacts

PD Dr. Eva Medina
Infection Immunology Research Group
Helmholtz Center for Infection Research
Inhoffenstrasse 7, DE–38124 Braunschweig (Germany)
Tel. +49 531 6181 4500, Fax +49 531 6181 4499, E-Mail eva.medina@helmholtz-hzi.de


 goto top of outline Article Information

Received: August 11, 2009
Accepted after revision: August 17, 2009
Published online: October 10, 2009
Number of Print Pages : 6
Number of Figures : 3, Number of Tables : 0, Number of References : 17
Additional supplementary material is available online - Number of Parts : 1


 goto top of outline Publication Details

Journal of Innate Immunity

Vol. 2, No. 1, Year 2010 (Cover Date: December 2009)

Journal Editor: Herwald H. (Lund), Egesten A. (Lund)
ISSN: 1662-811X (Print), eISSN: 1662-8128 (Online)

For additional information: http://www.karger.com/JIN


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Lowy FD: Antimicrobial resistance: the example of Staphylococcus aureus. J Clin Invest 2003;111:1265–1273.
  2. Boucher HW, Corey GR: Epidemiology of methicillin-resistant Staphylococcus aureus. Clin Infect Dis 2008;46(suppl 5):S344–S349.
  3. Frank MM, Fries LM: The role of complement in inflammation and phagocytosis. Immunol Today 1991;12:322–326.
  4. Guo RF, Ward PA: Role of C5a in inflammatory responses. Annu Rev Immunol 2005;23:821–852.
  5. Gasque P: Complement: a unique innate immune sensor for danger signals. Mol Immunol 2004;41:1089–1098.
  6. Cerquetti MC, Sordelli DO, Ortegon RA, Bellanti JA: Impaired lung defenses against Staphylococcus aureus in mice with hereditary deficiency of the fifth component of complement. Infect Immun 1983;41:1071–1076.
  7. Höpken UE, Lu B, Gerard NP, Gerard C: The C5a chemoattractant receptor mediates mucosal defence to infection. Nature 1996;383:86–89.
  8. Naber CK: Future strategies for treating Staphylococcus aureus bloodstream infections. Clin Microbiol Infect 2008;14(suppl 2):26–34.

    External Resources

  9. von Köckritz-Blickwede M, Rohde M, Oehmcke S, Miller LS, Cheung AL, Herwald H, Foster S, Medina E: Immunological mechanisms underlying the genetic predisposition to severe Staphylococcus aureus infection in the mouse model. Am J Pathol 2008;173:1657–1668.
  10. Nilsson UR, Müller-Eberhard HJ: Deficiency of the fifth component of complement in mice with an inherited complement defect. J Exp Med 1967;125:1–16.
  11. Jacobs JC, Miller ME: Fatal familial Leiner’s disease: a deficiency of the opsonic activity of serum complement. Pediatrics 1972;49:225–232.
  12. Delgado-Cerviño E, Fontán G, López-Trascasa M: C5 complement deficiency in a Spanish family: molecular characterization of the double mutation responsible for the defect. Mol Immunol 2005;42:105–111.

    External Resources

  13. Stevens JH, O’Hanley P, Shapiro JM, Mihm FG, Satoh PS, Collins JA, and Raffin TA: Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates. J Clin Invest 1986;77:1812–1816.
  14. Czermak BJ, Sarma V, Pierson CL, Warner RL, Huber-Lang M, Bless NM, Schmal H, Friedl HP, Ward PA: Protective effects of C5a blockade in sepsis. Nat Med 1999;5:788–792.
  15. Laudes IJ, Chu JC, Sikranth S, Huber-Lang M, Guo RF, Riedemann N, Sarma JV, Schmaier AH, Ward PA: Anti-C5a ameliorates coagulation/fibrinolytic protein changes in a rat model of sepsis. Am J Pathol 2002;160:1867–1875.
  16. Ward PA: Role of the complement in experimental sepsis. J Leukoc Biol 2008;83:467–470.
  17. Martin GS, Mannino DM, Eaton S, Moss M: The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003;348:1546–1554.