Surfactant protein-A-deficient mice display an exaggerated early inflammatory response to a β-resistant strain of influenza A virus

Gordon Li, Jiyauddin Siddiqui, Michael Hendry, Jennifer Akiyama, Jess Edmondson, Cynthia Brown, Lennell Allen, Stacey Levitt, Francis R Poulain, Samuel Hawgood

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Surfactant protein (SP)-A is a member of the collectin family of proteins. In vitro, SP-A binds influenza A virus (IAV), neutralizes infectivity, and enhances uptake by macrophages. SP-D also binds and neutralizes certain strains of IAV. To determine if SP-A has a role in protecting the intact animal against IAV infection, we inoculated gene-targeted SP-A-deficient mice (-/-) and littermate controls (+/+) with either saline or increasing doses of an IAV strain that binds SP-A but not SP-D. IAV was more virulent in SP-A-/- compared with +/+ mice, with a significantly lower mean lethal dose (LD50) and significantly greater weight loss during infection. SP-A-/mice also had increased airway epithelial injury and more alveolar cellular infiltrates than +/+ mice. On Day 2, SP-A-/mice had more neutrophils and higher MIP-2 levels in the lung than +/+ mice. We conclude the altered host response and increased susceptibility to X-79Δ167 infection in SP-A-/mice reflects a protective role for SP-A in regulating the host response to IAV. Because the recovery of virus from lung homogenates on Days 2 and 6 after inoculation was comparable in -/- and +/+ mice, we speculate SP-A reduces IAV virulence independently of direct viral neutralization.

Original languageEnglish (US)
Pages (from-to)277-282
Number of pages6
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume26
Issue number3
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Pulmonary and Respiratory Medicine

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    Li, G., Siddiqui, J., Hendry, M., Akiyama, J., Edmondson, J., Brown, C., Allen, L., Levitt, S., Poulain, F. R., & Hawgood, S. (2002). Surfactant protein-A-deficient mice display an exaggerated early inflammatory response to a β-resistant strain of influenza A virus. American Journal of Respiratory Cell and Molecular Biology, 26(3), 277-282.