Surfactant protein-A inhibits Aspergillus fumigatus-induced allergic T-cell responses.
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-gamma), 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 microg/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.


CONCLUSIONS
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.
Scanlon
Seth Thomas
ST
Pulmonary, Allergy and Critical Care Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA. sscanlon@uchicago.edu
Milovanova
Tatyana
T
Kierstein
Sonja
S
Cao
Yang
Y
Atochina
Elena N
EN
Tomer
Yaniv
Y
Russo
Scott J
SJ
Beers
Michael F
MF
Haczku
Angela
A
D000818:Animals; D001228:Aspergillosis / Q000276:immunology* / Q000473:pathology*; D001232:Aspergillus fumigatus / Q000276:immunology*; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology* / Q000276:immunology* / Q000382:microbiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D037662:Pulmonary Surfactant-Associated Protein A / Q000008:administration & dosage / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D037662:Pulmonary Surfactant-Associated Protein A