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 language | English (US) |
|---|---|
| Pages (from-to) | 6002-6011 |
| Number of pages | 10 |
| Journal | Infection and Immunity |
| Volume | 72 |
| Issue number | 10 |
| DOIs | |
| State | Published - Oct 2004 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Parasitology
- Microbiology
- Immunology
- Infectious Diseases
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 Franciska; 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 journal › Article
}
TY - JOUR
T1 - Enhanced lung injury and delayed clearance of Pneumocystis carinii in surfactant protein A-deficient mice
T2 - Attenuation of cytokine responses and reactive oxygen-nitrogen species
AU - Atochina, Elena N.
AU - Beck, James M.
AU - Preston, Angela M.
AU - Haczku, Angela Franciska
AU - Tomer, Yaniv
AU - Scanlon, Seth T.
AU - Fusaro, Trevor
AU - Casey, John
AU - Hawgood, Samuel
AU - Gow, Andrew J.
AU - Beers, Michael F.
PY - 2004/10
Y1 - 2004/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=4644334684&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4644334684&partnerID=8YFLogxK
U2 - 10.1128/IAI.72.10.6002-6011.2004
DO - 10.1128/IAI.72.10.6002-6011.2004
M3 - Article
C2 - 15385504
AN - SCOPUS:4644334684
VL - 72
SP - 6002
EP - 6011
JO - Infection and Immunity
JF - Infection and Immunity
SN - 0019-9567
IS - 10
ER -