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 language | English (US) |
|---|---|
| Pages (from-to) | 277-282 |
| Number of pages | 6 |
| Journal | American Journal of Respiratory Cell and Molecular Biology |
| Volume | 26 |
| Issue number | 3 |
| State | Published - 2002 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Surfactant protein-A-deficient mice display an exaggerated early inflammatory response to a β-resistant strain of influenza A virus
AU - Li, Gordon
AU - Siddiqui, Jiyauddin
AU - Hendry, Michael
AU - Akiyama, Jennifer
AU - Edmondson, Jess
AU - Brown, Cynthia
AU - Allen, Lennell
AU - Levitt, Stacey
AU - Poulain, Francis R
AU - Hawgood, Samuel
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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M3 - Article
VL - 26
SP - 277
EP - 282
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 3
ER -