SP-A enhances viral clearance and inhibits inflammation after pulmonary adenoviral infection.
Surfactant protein A (SP-A) is a member of the collectin family of host defense molecules expressed primarily in the epithelial cells of the lung. To determine the role of SP-A in pulmonary adenoviral infection, SP-A-deficient (SP-A -/-) mice were intratracheally infected with a replication-deficient recombinant adenovirus, Av1Luc1. Lung inflammation was markedly increased in SP-A -/- compared with SP-A +/+ mice and was associated with increased hemorrhage and epithelial cell injury. Polymorphonuclear cells in bronchoalveolar lavage fluid (BALF) were increased in SP-A -/- mice after administration of adenovirus. Coadministration of adenovirus and purified human SP-A ameliorated adenoviral-induced lung inflammation in SP-A -/- mice. Concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-1beta were increased in BALF of SP-A -/- mice. Likewise, TNF-alpha, IL-6, macrophage inflammatory protein (MIP)-1alpha, monocyte chemotactic protein-1, and MIP-2 mRNAs were increased in lung homogenates from SP-A -/- mice 6 and 24 h after viral administration. Clearance of adenoviral DNA from the lung and uptake of fluorescent-labeled adenovirus by alveolar macrophages were decreased in SP-A -/- mice. SP-A enhances viral clearance and inhibits lung inflammation during pulmonary adenoviral infection, providing support for the importance of SP-A in antiviral host defense.
Harrod
K S
KS
Children's Hospital Medical Center, Division of Neonatology and Pulmonary Biology, Cincinnati, Ohio 45229, USA.
Trapnell
B C
BC
Otake
K
K
Korfhagen
T R
TR
Whitsett
J A
JA
D000256:Adenoviridae / Q000302:isolation & purification*; D000257:Adenoviridae Infections / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000821:virology*; D016676:Macrophages, Alveolar / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout / Q000235:genetics; D011014:Pneumonia / Q000473:pathology / Q000517:prevention & control*; D011510:Proteolipids / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
D016207:Cytokines; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants