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

70 Citations (Scopus)

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

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Pulmonary Surfactant-Associated Protein A
Influenza A virus
Viruses
Pulmonary Surfactant-Associated Protein D
Collectins
Lung
Macrophages
Lethal Dose 50
Virus Diseases
Infection
Virulence
Weight Loss
Animals
Neutrophils
Genes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Pulmonary and Respiratory Medicine

Cite this

Surfactant protein-A-deficient mice display an exaggerated early inflammatory response to a β-resistant strain of influenza A virus. / Li, Gordon; Siddiqui, Jiyauddin; Hendry, Michael; Akiyama, Jennifer; Edmondson, Jess; Brown, Cynthia; Allen, Lennell; Levitt, Stacey; Poulain, Francis R; Hawgood, Samuel.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 26, No. 3, 2002, p. 277-282.

Research output: Contribution to journalArticle

Li, G, Siddiqui, J, Hendry, M, Akiyama, J, Edmondson, J, Brown, C, Allen, L, Levitt, S, Poulain, FR & 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, vol. 26, no. 3, pp. 277-282.
Li, Gordon ; Siddiqui, Jiyauddin ; Hendry, Michael ; Akiyama, Jennifer ; Edmondson, Jess ; Brown, Cynthia ; Allen, Lennell ; Levitt, Stacey ; Poulain, Francis R ; Hawgood, Samuel. / Surfactant protein-A-deficient mice display an exaggerated early inflammatory response to a β-resistant strain of influenza A virus. In: American Journal of Respiratory Cell and Molecular Biology. 2002 ; Vol. 26, No. 3. pp. 277-282.
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