Delayed clearance of pneumocystis carinii infection, increased inflammation, and altered nitric oxide metabolism in lungs of surfactant protein-D knockout mice.
Surfactant protein-D (SP-D), a member of the "collectin" family, has been shown to play a role in innate immunity through modulation of inflammation and clearance of organisms. The role of SP-D in host defense against Pneumocystis carinii pneumonia was assessed using SP-D knockout (KO) mice. When inoculated with P. carinii, both wild-type (wt) and SP-D KO mice required CD4 cell depletion to develop infection. In CD4 cell-depleted models, 2 weeks after infection with P. carinii, SP-D KO mice developed increased intensity of infection, compared with wt mice, despite higher lung-inflammation scores and increased amounts of alveolar inflammatory cells. The increased inflammation seen in SP-D KO mice was accompanied by increases in lung weight, expression of inducible nitric oxide (NO) synthase, total NO levels, and 3-nitrotyrosine levels in lung tissue. These results indicate that SP-D plays a role in host defense against P. carinii in vivo by modulating clearance of organisms, lung inflammation, and metabolism of NO.
Atochina
Elena N
EN
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6061, USA.
Gow
Andrew J
AJ
Beck
James M
JM
Haczku
Angela
A
Inch
Adam
A
Kadire
Helchem
H
Tomer
Yaniv
Y
Davis
Christine
C
Preston
Angela M
AM
Poulain
Francis
F
Hawgood
Samuel
S
Beers
Michael F
MF
D000818:Animals; D015152:Blotting, Northern; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology / Q000382:microbiology; D005260:Female; D006651:Histocytochemistry; D008168:Lung / Q000276:immunology / Q000473:pathology; D008212:Lymphocyte Depletion; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D045363:Pneumocystis carinii / Q000235:genetics / Q000276:immunology*; D011020:Pneumonia, Pneumocystis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D037663:Pulmonary Surfactant-Associated Protein D / Q000235:genetics / Q000276:immunology*; D011663:Pulmonary Surfactants / Q000276:immunology*; D012329:RNA, Bacterial / Q000737:chemistry / Q000235:genetics; D013047:Specific Pathogen-Free Organisms; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism
D037663:Pulmonary Surfactant-Associated Protein D; D011663:Pulmonary Surfactants; D012329:RNA, Bacterial; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse