Inhibition of complement activation alleviates acute lung injury induced by highly pathogenic avian influenza H5N1 virus infection

Am J Respir Cell Mol Biol. 2013 Aug;49(2):221-30. doi: 10.1165/rcmb.2012-0428OC.


The acute lung injury (ALI) that occurs after the highly pathogenic avian influenza H5N1 virus infection is associated with an abnormal host innate immune response. Because the complement system plays a central role in innate immunity and because aberrant complement activation is associated with a variety of autoimmune and inflammatory diseases, we investigated the complement involvement in the pathogenesis of ALI induced by H5N1 virus infection. We showed that ALI in H5N1-infected mice was caused by excessive complement activation, as demonstrated by deposition of C3, C5b-9, and mannose-binding lectin (MBL)-C in lung tissue, and by up-regulation of MBL-associated serine protease-2 and the complement receptors C3aR and C5aR. Treatment of H5N1-infected mice with a C3aR antagonist led to significantly reduced inflammation in lungs, alleviating ALI. Furthermore, complement inhibition with an anti-C5a antibody or complement depletion with cobra venom factor after H5N1 challenge resulted in a similar level of protection to that seen in C3aR antagonist-treated mice. These results indicate that excessive complement activation plays an important role in mediating H5N1-induced ALI and that inhibition of complement may be an effective clinical intervention and adjunctive treatment for H5N1-induced ALI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / metabolism*
  • Acute Lung Injury / pathology
  • Acute Lung Injury / prevention & control
  • Acute Lung Injury / virology
  • Animals
  • Antibodies / pharmacology
  • Complement Activation*
  • Complement System Proteins / metabolism*
  • Elapid Venoms / pharmacology
  • Female
  • Influenza A Virus, H5N1 Subtype / metabolism*
  • Lung / metabolism*
  • Lung / pathology
  • Lung / virology
  • Mice
  • Orthomyxoviridae Infections / metabolism*
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / prevention & control
  • Receptor, Anaphylatoxin C5a / metabolism*
  • Receptors, Complement / metabolism*


  • Antibodies
  • Elapid Venoms
  • Receptor, Anaphylatoxin C5a
  • Receptors, Complement
  • complement C3a receptor
  • Complement System Proteins