Attenuated allergic airway hyperresponsiveness in C57BL/6 mice is associated with enhanced surfactant protein (SP)-D production following allergic sensitization.
BACKGROUND
C57BL/6 mice have attenuated allergic airway hyperresponsiveness (AHR) when compared with Balb/c mice but the underlying mechanisms remain unclear. SP-D, an innate immune molecule with potent immunosuppressive activities may have an important modulatory role in the allergic airway response and the consequent physiological changes. We hypothesized that an elevated SP-D production is associated with the impaired ability of C57BL/6 mice to develop allergic AHR.


METHODS
SP-D mRNA and protein expression was investigated during development of allergic airway changes in a model of Aspergillus fumigatus (Af)-induced allergic inflammation. To study whether strain dependency of allergic AHR is associated with different levels of SP-D in the lung, Balb/c and C57BL/6 mice were compared.


RESULTS
Sensitization and exposure to Af induced significant airway inflammation in both mouse strains in comparison with naïve controls. AHR to acetylcholine however was significantly attenuated in C57BL/6 mice in spite of increased eosinophilia and serum IgE when compared with Balb/c mice (p < 0.05). Af challenge of sensitized C57BL/6 mice induced a markedly increased SP-D protein expression in the SA surfactant fraction (1,894 +/- 170% of naïve controls) that was 1.5 fold greater than the increase in Balb/c mice (1,234 +/- 121% p < 0.01). These changes were selective since levels of the hydrophobic SP-B and SP-C and the hydrophilic SP-A were significantly decreased following sensitization and challenge with Af in both strains. Further, sensitized and exposed C57BL/6 mice had significantly lower IL-4 and IL-5 in the BAL fluid than that of Balb/c mice (p < 0.05).


CONCLUSIONS
These results suggest that enhanced SP-D production in the lung of C57BL/6 mice may contribute to an attenuated AHR in response to allergic airway sensitization. SP-D may act by inhibiting synthesis of Th2 cytokines.
Atochina
Elena N
EN
Pulmonary, Allergy & Critical Care Division, Department of Medicine, University of Pennsylvania, School of Medicine, Philadelphia, PA, USA. haczku@mail.med.upenn.edu
Beers
Michael F
MF
Tomer
Yaniv
Y
Scanlon
Seth T
ST
Russo
Scott J
SJ
Panettieri
Reynold A
RA
Haczku
Angela
A
D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology; D000818:Animals; D001232:Aspergillus fumigatus / Q000737:chemistry / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000209:etiology* / Q000276:immunology / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002457:Cell Extracts / Q000008:administration & dosage / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D004198:Disease Susceptibility; D005260:Female; D006967:Hypersensitivity / Q000150:complications* / Q000276:immunology*; D007114:Immunization; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D037663:Pulmonary Surfactant-Associated Protein D / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012140:Respiratory Tract Diseases / Q000276:immunology; D018418:Th2 Cells / Q000378:metabolism
D000485:Allergens; D002457:Cell Extracts; D016207:Cytokines; D037663:Pulmonary Surfactant-Associated Protein D; D012333:RNA, Messenger