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A novel role for lung surfactant protein-D in allergic sensitization

Presented at the Neonatal Society 2007 Summer Meeting (programme).

Deb R1, Mackay R-M2, Reid K1, Clark H2

1 1MRC Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK
2 Division of Child Health, University of Southampton. Southampton General Hospital, Southampton SO16 6YD, UK

Background: The major house dust mite (HDM) allergen Der p 1 has been detected in both umbilical cord blood and in amniotic fluid, indicating fetal exposure to allergens (1). Lung Surfactant Protein-D (SP-D) belongs to the collectin family of carbohydrate-binding proteins, and has been shown to downregulate allergic hypersensitivity in mice (2,3). Diminished levels of SP-D at both the fetal and neonatal stage may enhance susceptibility to the development of allergic diseases.

Aim: To determine whether the presence of SP-D, at the time of primary allergen exposure, could downregulate allergic hypersensitivity, on subsequent allergen challenge.

Methods: We determined the effects of co-administration of a recombinant fragment of SP-D (rfhSP-D) with HDM allergens, to BALB/C mice, on the development of allergy on subsequent (secondary) allergen exposure. All work was undertaken in accordance with UK ethical guidelines.

Results: In a mouse model of allergic hypersensitivity to the house dust mite Dermatophagoides pteronnysinus, treatment with rfhSP-D at the time of primary allergen exposure resulted in diminished airway hyperresponsiveness and reduced eosiniphilic infiltration into the lungs, on subsequent allergen challenge. Cultured splenocytes from mice treated with rfhSP-D at the time of primary allergen exposure also produced increased levels of IFN-γ, and decreased levels of IL-4, and IL-13 compared to untreated controls, corresponding to a shift in cytokine profile from Th2 (typical of an allergic response) to Th1. Furthermore, there was a decrease in serum IgE levels, and increase in serum IgG levels with rfhSP-D treatment, suggesting a role for SP-D in switching the type of antibody response generated.

Conclusions: These data suggest a novel, protective role for SP-D in allergic sensitization, and a therapeutic potential of SP-D in the prevention of allergic disease, notably for neonates who are exposed to allergens and have diminished levels of surfactant proteins.

1. Holloway JA, Warner JO, Vance GH, Diaper ND, Warner JA, Jones CA. (2000) Lancet 356(9245):1900-2
2. Strong P, Townsend P, Mackay R, Reid KB, Clark HW. (2003) Clin Exp Immunol. 134,181- 7
3. Singh M, Madan T, Waters,P, Parida SK, Sarma,PU, Kishore,U. (2003) Immunol Lett. 86, 299-307

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