Surfactant proteins A and D enhance pulmonary clearance of Pseudomonas aeruginosa.
Surfactant protein (SP)-A and SP-D, members of the collectin family, are involved in innate host defenses against various bacterial and viral pathogens. In this study, we asked whether SP-A and SP-D enhance clearance of a nonmucoid strain of Pseudomonas aeruginosa from the lungs. We infected mice deficient in SP-A (SP-A-/-), SP-D (SP-D-/-) and both pulmonary collectins (SP-AD-/-) by intratracheal administration of P. aeruginosa. Six hours after infection, bacterial counts were significantly higher in SP-A-/-, SP-D-/-, and SP-AD-/- compared with wild-type (WT) mice. Forty-eight hours after infection, bacterial counts were significantly higher in SP-A-/- mice compared with WT mice and in SP-AD-/- mice compared with WT, SP-A-/-, and SP-D-/- mice. Phagocytosis of the bacteria by alveolar macrophages was decreased in SP-A-/- and SP-D-/- mice. Levels of macrophage inflammatory peptide-2 and IL-6 were more elevated in the lungs of SP-D and SP-AD-/- mice compared with WT mice. There was more infiltration by neutrophils in the lungs of SP-D-/- compared with WT and SP-A-/- mice 48 h after infection. This study shows that SP-A and SP-D enhance pulmonary clearance of P. aeruginosa by stimulating phagocytosis by alveolar macrophages and by modulating the inflammatory response in the lungs. These findings also show that the functions of SP-A and SP-D are not completely redundant in vivo.
Giannoni
Eric
E
Department of Pediatrics, Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143-0110, USA.
Sawa
Teiji
T
Allen
Lennell
L
Wiener-Kronish
Jeanine
J
Hawgood
Sam
S
D000818:Animals; D002478:Cells, Cultured; D054426:Chemokine CXCL2; D015169:Colony Count, Microbial; D015850:Interleukin-6 / Q000096:biosynthesis; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015846:Monokines / Q000096:biosynthesis; D020556:Neutrophil Infiltration; D010587:Phagocytosis; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000382:microbiology; D011552:Pseudomonas Infections / Q000276:immunology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000302:isolation & purification*; D037662:Pulmonary Surfactant-Associated Protein A / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology
D054426:Chemokine CXCL2; D015850:Interleukin-6; D015846:Monokines; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D011994:Recombinant Proteins