Enhanced Lung Injury and Delayed Clearance of
Pneumocystis carinii
in Surfactant Protein A-Deficient Mice: Attenuation of Cytokine Responses and Reactive Oxygen-Nitrogen Species
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Published:2004-10
Issue:10
Volume:72
Page:6002-6011
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ISSN:0019-9567
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Container-title:Infection and Immunity
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language:en
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Short-container-title:Infect Immun
Author:
Atochina Elena N.1, Beck James M.2, Preston Angela M.2, Haczku Angela1, Tomer Yaniv1, Scanlon Seth T.1, Fusaro Trevor3, Casey John3, Hawgood Samuel4, Gow Andrew J.3, Beers Michael F.1
Affiliation:
1. Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania School of Medicine 2. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School and Veterans Affairs Medical Center, Ann Arbor, Michigan 3. Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 4. Division of Neonatology, University of California at San Francisco, San Francisco, California
Abstract
ABSTRACT
Surfactant protein A (SP-A), a member of the collectin family, selectively binds to
Pneumocystis carinii
and mediates interactions between pathogen and host alveolar macrophages in vitro. To test the hypothesis that mice lacking SP-A have delayed clearance of
Pneumocystis
organisms and enhanced lung injury, wild-type C57BL/6 (WT) and SP-A-deficient mice (SP-A
−/−
) with or without selective CD4
+
-T-cell depletion were intratracheally inoculated with
Pneumocystis
organisms. Four weeks later, CD4-depleted SP-A-deficient mice had developed a more severe
Pneumocystis
infection than CD4-depleted WT (
P. carinii
pneumonia [PCP] scores of 3 versus 2, respectively). Whereas all non-CD4-depleted WT mice were free of PCP, intact SP-A
−/−
mice also had evidence of increased organism burden.
Pneumocystis
infection in SP-A-deficient mice was associated histologically with enhanced peribronchial and/or perivascular cellularity (score of 4 versus 2, SP-A
−/−
versus C57BL/6 mice, respectively) and a corresponding increase in bronchoalveolar lavage (BAL) cell counts. Increases in SP-D content, gamma interferon, interleukin-4, interleukin-5, and tumor necrosis factor alpha in BAL fluid occurred but were attenuated in PCP-infected SP-A
−/−
mice compared to WT mice. There were increases in total BAL NO levels in both infected groups, but nitrite levels were higher in SP-A
−/−
mice, indicating a reduction in production of higher oxides of nitrogen that was also reflected in lower levels of 3-nitrotyrosine staining in the SP-A
−/−
group. We conclude that despite increases in inflammatory cells, SP-A-deficient mice infected with
P. carinii
exhibit an enhanced susceptibility to the organism and attenuated production of proinflammatory cytokines and reactive oxygen-nitrogen species. These data support the concept that SP-A is a local effector molecule in the lung host defense against
P. carinii
in vivo.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Reference69 articles.
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