Enhanced lung injury and delayed clearance of Pneumocystis carinii in surfactant protein A-deficient mice

Attenuation of cytokine responses and reactive oxygen-nitrogen species

Elena N. Atochina, James M. Beck, Angela M. Preston, Angela Haczku, Yaniv Tomer, Seth T. Scanlon, Trevor Fusaro, John Casey, Samuel Hawgood, Andrew J. Gow, Michael F. Beers

Research output: Contribution to journalArticle

52 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6002-6011
Number of pages10
JournalInfection and Immunity
Volume72
Issue number10
DOIs
Publication statusPublished - Oct 2004
Externally publishedYes

Fingerprint

Pulmonary Surfactant-Associated Protein A
Reactive Nitrogen Species
Pneumocystis carinii
Lung Injury
Reactive Oxygen Species
Cytokines
Pneumocystis Pneumonia
Inbred C57BL Mouse
Pneumocystis
Pneumocystis Infections
Bronchoalveolar Lavage
Collectins
Pulmonary Surfactant-Associated Protein D
Nitrogen Oxides
Host-Pathogen Interactions
Interleukin-5
Bronchoalveolar Lavage Fluid
Alveolar Macrophages
Nitrites
Interleukin-4

ASJC Scopus subject areas

  • Immunology

Cite this

Enhanced lung injury and delayed clearance of Pneumocystis carinii in surfactant protein A-deficient mice : Attenuation of cytokine responses and reactive oxygen-nitrogen species. / Atochina, Elena N.; Beck, James M.; Preston, Angela M.; Haczku, Angela; Tomer, Yaniv; Scanlon, Seth T.; Fusaro, Trevor; Casey, John; Hawgood, Samuel; Gow, Andrew J.; Beers, Michael F.

In: Infection and Immunity, Vol. 72, No. 10, 10.2004, p. 6002-6011.

Research output: Contribution to journalArticle

Atochina, EN, Beck, JM, Preston, AM, Haczku, A, Tomer, Y, Scanlon, ST, Fusaro, T, Casey, J, Hawgood, S, Gow, AJ & Beers, MF 2004, 'Enhanced lung injury and delayed clearance of Pneumocystis carinii in surfactant protein A-deficient mice: Attenuation of cytokine responses and reactive oxygen-nitrogen species', Infection and Immunity, vol. 72, no. 10, pp. 6002-6011. https://doi.org/10.1128/IAI.72.10.6002-6011.2004
Atochina, Elena N. ; Beck, James M. ; Preston, Angela M. ; Haczku, Angela ; Tomer, Yaniv ; Scanlon, Seth T. ; Fusaro, Trevor ; Casey, John ; Hawgood, Samuel ; Gow, Andrew J. ; Beers, Michael F. / Enhanced lung injury and delayed clearance of Pneumocystis carinii in surfactant protein A-deficient mice : Attenuation of cytokine responses and reactive oxygen-nitrogen species. In: Infection and Immunity. 2004 ; Vol. 72, No. 10. pp. 6002-6011.
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AU - Preston, Angela M.

AU - Haczku, Angela

AU - Tomer, Yaniv

AU - Scanlon, Seth T.

AU - Fusaro, Trevor

AU - Casey, John

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