Surfactant protein D inhibits early airway response in Aspergillus fumigatus-sensitized mice.
BACKGROUND
The surfactant protein SP-D has been reported to reduce bronchial hyper-responsiveness, blood eosinophilia, and T-helper type 2 cytokines in models of allergic asthma. However, little is known about the functional effect of SP-D on the early airway response upon allergen inhalation, which is an important feature of this disease.


OBJECTIVE
We investigated whether SP-D is able to reduce the immediate allergen-induced mediator release and the early bronchial obstruction in addition to its effects on airway inflammation and bronchial hyperresponsiveness in an Aspergillus fumigatus mouse asthma model.


METHODS
A. fumigatus-sensitized mice were treated with a recombinant fragment of human SP-D or placebo. Lung functions were measured in orotracheally intubated, spontaneously breathing animals using body plethysmography. In addition, passively sensitized precision-cut lung slices (PCLS) were used to determine the effect of SP-D on allergen-induced histamine release.


RESULTS
SP-D inhibited the allergen-induced early airway response and reduced airway hyperresponsiveness compared with placebo. Eosinophilia in bronchoalveolar lavage and lung tissue was reduced after SP-D treatment, possibly by reducing eotaxin levels in the lung. Furthermore, SP-D treatment reduced the allergen-induced histamine release from PCLS.


CONCLUSIONS
These data suggest that SP-D not only reduces allergen-induced eosinophilic inflammation and airway hyperresponsiveness but also provides protection against early airway obstruction by inhibition of early mediator release.
Erpenbeck
V J
VJ
Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany.
Ziegert
M
M
Cavalet-Blanco
D
D
Martin
C
C
Baelder
R
R
Glaab
T
T
Braun
A
A
Steinhilber
W
W
Luettig
B
B
Uhlig
S
S
Hoymann
H G
HG
Krug
N
N
Hohlfeld
J M
JM
D000280:Administration, Inhalation; D000485:Allergens / Q000276:immunology*; D000818:Animals; D000946:Antigens, Fungal / Q000276:immunology; D001232:Aspergillus fumigatus / Q000276:immunology*; D001249:Asthma / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000378:metabolism; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004802:Eosinophilia / Q000517:prevention & control; D005260:Female; D006636:Histamine Release / Q000187:drug effects; D007073:Immunoglobulin E / Q000097:blood; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008170:Lung Compliance; D051379:Mice; D008807:Mice, Inbred BALB C; D037663:Pulmonary Surfactant-Associated Protein D / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use
D000485:Allergens; D000946:Antigens, Fungal; C515456:CCL11 protein, human; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D015848:Interleukin-5; D037663:Pulmonary Surfactant-Associated Protein D; D011994:Recombinant Proteins; D007073:Immunoglobulin E