title: Inhibition of complement activation alleviates acute lung injury induced by highly pathogenic avian influenza H5N1 virus infection.
abstract: 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.
authors.affiliation: 1 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Sun
authors.forename: Guangyu
authors.initials: G
authors.lastname: Zhao
authors.forename: Chenfeng
authors.initials: C
authors.lastname: Liu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Hongbin
authors.initials: H
authors.lastname: Song
authors.forename: Lanying
authors.initials: L
authors.lastname: Du
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.forename: Renfeng
authors.initials: R
authors.lastname: Guo
authors.forename: Stephen
authors.initials: S
authors.lastname: Tomlinson
authors.forename: Yusen
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control / Q000821:virology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D003167:Complement Activation; D003165:Complement System Proteins / Q000378:metabolism*; D004546:Elapid Venoms / Q000494:pharmacology; D005260:Female; D053124:Influenza A Virus, H5N1 Subtype / Q000378:metabolism*; D008168:Lung / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D044087:Receptor, Anaphylatoxin C5a / Q000378:metabolism*; D011951:Receptors, Complement / Q000378:metabolism*
chemical_list: D000906:Antibodies; D004546:Elapid Venoms; D044087:Receptor, Anaphylatoxin C5a; D011951:Receptors, Complement; C085567:complement C3a receptor; D003165:Complement System Proteins