Macrophage dysfunction and susceptibility to pulmonary Pseudomonas aeruginosa infection in surfactant protein C-deficient mice.
To determine the role of surfactant protein C (SP-C) in host defense, SP-C-deficient (Sftpc-/-) mice were infected with the pulmonary pathogen Pseudomonas aeruginosa by intratracheal injection. Survival of young, postnatal day 14 Sftpc-/- mice was decreased in comparison to Sftpc+/+ mice. The sensitivity to Pseudomonas bacteria was specific to the 129S6 strain of Sftpc-/- mice, a strain that spontaneously develops interstitial lung disease-like lung pathology with age. Pulmonary bacterial load and leukocyte infiltration were increased in the lungs of Sftpc-/- mice 24 h after infection. Early influx of polymorphonuclear leukocytes in the lungs of uninfected newborn Sftpc-/- mice relative to Sftpc+/+ mice indicate that the lack of SP-C promotes proinflammatory responses in the lung. Mucin expression, as indicated by Alcian blue staining, was increased in the airways of Sftpc-/- mice following infection. Phagocytic activity of alveolar macrophages from Sftpc-/- mice was reduced. The uptake of fluorescent beads in vitro and the number of bacteria phagocytosed by alveolar macrophages in vivo was decreased in the Sftpc-/- mice. Alveolar macrophages from Sftpc-/- mice expressed markers of alternative activation that are associated with diminished pathogen response and advancing pulmonary fibrosis. These findings implicate SP-C as a modifier of alveolar homeostasis. SP-C plays an important role in innate host defense of the lung, enhancing macrophage-mediated Pseudomonas phagocytosis, clearance and limiting pulmonary inflammatory responses.
Glasser
Stephan W
SW
Division of Pulmonary Biology, Department of Pediatrics, Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, USA. steve.glasser@cchmc.org
Senft
Albert P
AP
Whitsett
Jeffrey A
JA
Maxfield
Melissa D
MD
Ross
Gary F
GF
Richardson
Theresa R
TR
Prows
Daniel R
DR
Xu
Yan
Y
Korfhagen
Thomas R
TR
D000818:Animals; D015415:Biomarkers; D004195:Disease Models, Animal; D006965:Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis; D011552:Pseudomonas Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D037721:Pulmonary Surfactant-Associated Protein C / Q000172:deficiency* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D015996:Survival Rate
D015415:Biomarkers; D037721:Pulmonary Surfactant-Associated Protein C