Surfactant protein-A inhibits Aspergillus fumigatus-induced allergic T-cell responses

Seth Thomas Scanlon, Tatyana Milovanova, Sonja Kierstein, Yang Cao, Elena Nikolaevna Atochina, Yaniv Tomer, Scott J. Russo, Michael F. Beers, Angela Haczku

Research output: Contribution to journalArticle

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Abstract

Background: The pulmonary surfactant protein (SP)-A has potent immunomodulatory activities but its role and regulation during allergic airway inflammation is unknown. Methods: We studied changes in SP-A expression in the bronchoalveolar lavage (BAL) using a murine model of single Aspergillus fumigatus (Af) challenge of sensitized animals. Results: SP-A protein levels in the BAL fluid showed a rapid, transient decline that reached the lowest values (25% of controls) 12 h after intranasal Af provocation of sensitized mice. Decrease of SP-A was associated with influx of inflammatory cells and increase of IL-4 and IL-5 mRNA and protein levels. Since levels of SP-A showed a significant negative correlation with these BAL cytokines (but not with IFN-γ), we hypothesized that SP-A exerts an inhibitory effect on Th2-type immune responses. To study this hypothesis, we used an in vitro Af-rechallenge model. Af-induced lymphocyte proliferation of cells isolated from sensitized mice was inhibited in a dose-dependent manner by addition of purified human SP-A (0.1-10 μg/ml). Flow cytometric studies on Af-stimulated lymphocytes indicated that the numbers of CD4+ (but not CD8+) T cells were significantly increased in the parental population and decreased in the third and fourth generation in the presence of SP-A. Further, addition of SP-A to the tissue culture inhibited Af-induced IL-4 and IL-5 production suggesting that SP-A directly suppressed allergen-stimulated CD4+ T cell function. Conclusion: We speculate that a transient lack of this lung collectin following allergen exposure of the airways may significantly contribute to the development of a T-cell dependent allergic immune response.

Original languageEnglish
Article number97
JournalRespiratory Research
Volume6
DOIs
Publication statusPublished - 24 Aug 2005
Externally publishedYes

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Pulmonary Surfactant-Associated Protein A
Aspergillus fumigatus
T-Lymphocytes
Interleukin-5
Bronchoalveolar Lavage
Interleukin-4
Allergens
Pulmonary Surfactant-Associated Proteins
Collectins
Bronchoalveolar Lavage Fluid
Lymphocyte Count
Proteins
Cell Proliferation
Lymphocytes

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Medicine(all)

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Surfactant protein-A inhibits Aspergillus fumigatus-induced allergic T-cell responses. / Scanlon, Seth Thomas; Milovanova, Tatyana; Kierstein, Sonja; Cao, Yang; Atochina, Elena Nikolaevna; Tomer, Yaniv; Russo, Scott J.; Beers, Michael F.; Haczku, Angela.

In: Respiratory Research, Vol. 6, 97, 24.08.2005.

Research output: Contribution to journalArticle

Scanlon, ST, Milovanova, T, Kierstein, S, Cao, Y, Atochina, EN, Tomer, Y, Russo, SJ, Beers, MF & Haczku, A 2005, 'Surfactant protein-A inhibits Aspergillus fumigatus-induced allergic T-cell responses', Respiratory Research, vol. 6, 97. https://doi.org/10.1186/1465-9921-6-97
Scanlon, Seth Thomas ; Milovanova, Tatyana ; Kierstein, Sonja ; Cao, Yang ; Atochina, Elena Nikolaevna ; Tomer, Yaniv ; Russo, Scott J. ; Beers, Michael F. ; Haczku, Angela. / Surfactant protein-A inhibits Aspergillus fumigatus-induced allergic T-cell responses. In: Respiratory Research. 2005 ; Vol. 6.
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T1 - Surfactant protein-A inhibits Aspergillus fumigatus-induced allergic T-cell responses

AU - Scanlon, Seth Thomas

AU - Milovanova, Tatyana

AU - Kierstein, Sonja

AU - Cao, Yang

AU - Atochina, Elena Nikolaevna

AU - Tomer, Yaniv

AU - Russo, Scott J.

AU - Beers, Michael F.

AU - Haczku, Angela

PY - 2005/8/24

Y1 - 2005/8/24

N2 - Background: The pulmonary surfactant protein (SP)-A has potent immunomodulatory activities but its role and regulation during allergic airway inflammation is unknown. Methods: We studied changes in SP-A expression in the bronchoalveolar lavage (BAL) using a murine model of single Aspergillus fumigatus (Af) challenge of sensitized animals. Results: SP-A protein levels in the BAL fluid showed a rapid, transient decline that reached the lowest values (25% of controls) 12 h after intranasal Af provocation of sensitized mice. Decrease of SP-A was associated with influx of inflammatory cells and increase of IL-4 and IL-5 mRNA and protein levels. Since levels of SP-A showed a significant negative correlation with these BAL cytokines (but not with IFN-γ), we hypothesized that SP-A exerts an inhibitory effect on Th2-type immune responses. To study this hypothesis, we used an in vitro Af-rechallenge model. Af-induced lymphocyte proliferation of cells isolated from sensitized mice was inhibited in a dose-dependent manner by addition of purified human SP-A (0.1-10 μg/ml). Flow cytometric studies on Af-stimulated lymphocytes indicated that the numbers of CD4+ (but not CD8+) T cells were significantly increased in the parental population and decreased in the third and fourth generation in the presence of SP-A. Further, addition of SP-A to the tissue culture inhibited Af-induced IL-4 and IL-5 production suggesting that SP-A directly suppressed allergen-stimulated CD4+ T cell function. Conclusion: We speculate that a transient lack of this lung collectin following allergen exposure of the airways may significantly contribute to the development of a T-cell dependent allergic immune response.

AB - Background: The pulmonary surfactant protein (SP)-A has potent immunomodulatory activities but its role and regulation during allergic airway inflammation is unknown. Methods: We studied changes in SP-A expression in the bronchoalveolar lavage (BAL) using a murine model of single Aspergillus fumigatus (Af) challenge of sensitized animals. Results: SP-A protein levels in the BAL fluid showed a rapid, transient decline that reached the lowest values (25% of controls) 12 h after intranasal Af provocation of sensitized mice. Decrease of SP-A was associated with influx of inflammatory cells and increase of IL-4 and IL-5 mRNA and protein levels. Since levels of SP-A showed a significant negative correlation with these BAL cytokines (but not with IFN-γ), we hypothesized that SP-A exerts an inhibitory effect on Th2-type immune responses. To study this hypothesis, we used an in vitro Af-rechallenge model. Af-induced lymphocyte proliferation of cells isolated from sensitized mice was inhibited in a dose-dependent manner by addition of purified human SP-A (0.1-10 μg/ml). Flow cytometric studies on Af-stimulated lymphocytes indicated that the numbers of CD4+ (but not CD8+) T cells were significantly increased in the parental population and decreased in the third and fourth generation in the presence of SP-A. Further, addition of SP-A to the tissue culture inhibited Af-induced IL-4 and IL-5 production suggesting that SP-A directly suppressed allergen-stimulated CD4+ T cell function. Conclusion: We speculate that a transient lack of this lung collectin following allergen exposure of the airways may significantly contribute to the development of a T-cell dependent allergic immune response.

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