Role of Surfactant protein D in Murine and Human Allergic Airway Response

E.B. Brandt1, E.E. Muntel2, G.K. Hershey1, M. Stevenson3, J.A. Whitsett1, M.E. Rothenberg1

Author address: 

1 Cincinnati Children's Hospital Medical Center, Cincinnati, OH 2 University of Cincinnati, Cincinnati, OH 3 Akron Children's Hospital, Akron, OH


RATIONALE: Surfactant protein D (SP-D) has been implicated in host defense and is thought to be protective during allergic airway reactions. We were interested in elucidating the immunological function of SP-D during allergic pulmonary inflammation. METHODS: Baseline humoral and cellular responses were assessed in SP-D gene deficient mice (SP-D-/-) and their controls. Immune and inflammatory responses were also collected 18-72h following repeated intranasal doses of Aspergillus fumigatus (ASP). Finally, the effect of a single nucleotide polymorphism (SNP) replacing a methionine by a threonine was studied in a population of asthmatics and controls. RESULTS: Measurements of total serum immunoglobulin levels in SP-D-/- mice revealed increased IgG2a when compared to control mice. Additionally, stimulation of splenocytes with anti-CD3/CD28 induced markedly decreased Th2 cytokines (IL-4, IL-5, IL-10, IL-13) in young SP-D-/- mice. Accordingly, intranasal sensitization with ASP followed one week later by 1-2 intranasal ASP challenges, resulted in a modest decrease in BALF eosinophilia in SP-D-/- compared to control mice. This effect was no longer observed after 9 challenges over a three-week period. Finally, the prevalence of a SNP within the human SP-D gene, proven to affect pathogen binding, was not significantly different between asthmatic patients and the general population. However, the frequency of the Thr/Thr mutation appeared to diminish with disease severity. CONCLUSIONS: The absence of SP-D results in impaired Th2 responses in young mice both at baseline and following allergen challenge. Additionally, a SNP-induced functional defect in human SP-D might diminish disease severity in asthmatic patients.

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Full conference title: 

2006 American Academy of Allergy, Asthma, and Immunology Annual Meeting
    • AAAAI 2006 (62nd)