A recombinant fragment of human SP-D reduces allergic responses in mice sensitized to house dust mite allergens

Abstract

C57Bl6 mice sensitized to Dermatophagoides pteronyssinus and challenged with D. pteronyssinus allergen extract given intranasally followed by treatment with intranasal applications of a 60-kDa truncated, trimeric recombinant form of human SP-D (rfhSP-D) showed a significant reduction in serum IgE, IgG1, peripheral blood eosinophilia and airway hyperresponsiveness compared to saline or bovine serum albumin-treated controls. Intracellular cytokine staining of lung and spleen homogenates showed increases in interleukin (IL)-12 production in lung tissue and normalization of IL-12 and interferon (IFN)-gamma in spleen tissue. In previous studies we demonstrated the effectiveness of native SP-D and rfhSP-D in down-regulating allergic responses to allergens of Aspergillus fumigatus. The results reported here indicate that rfhSP-D can suppress the development of allergic symptoms in sensitized mice challenged with allergens of the common house dust mite.

Fig. 1

Total serum IgE measured after treatment with five daily doses of PBS (HP), 10 µg rfhSP-D (HR) or BSA (HB), given after Der p challenge. P = non-sensitized mice treated with PBS.

Fig. 2

D. pteronyssinus-specific IgG1 after treatment with five daily doses of PBS (HP), 10 µg rfhSP-D (HR) or BSA (HB), given after allergen challenge.

Fig. 3

Effect of treatment with four doses of PBS (HP), 10 µg rfhSP-D (HR) or BSA (HB) on peripheral blood eosinophilia in allergen challenged mice. P = non-sensitized mice treated with PBS.

Fig. 4

IL-12 measured in the lungs 1 day after allergen re-challenge given 4 days after completion of treatment of allergen-challenged mice with four daily doses of PBS (HP) or 10 µg rfhSP-D (HR). P = non-sensitized mice treated with PBS.

Fig. 5

IL-12 measured in the spleens taken 1 day after allergen re-challenge given 4 days after completion of treatment of allergen-challenged mice with four daily doses of PBS (HP) or 10 µg rfhSP-D (HR). P = non-sensitized mice treated with PBS.

Fig. 6

IFN-γ measured in the spleens taken 1 day after allergen re-challenge given 4 days after completion of treatment of allergen-challenged mice with four daily doses of PBS (HP) or 10 µg rfhSP-D (HR). P = non-sensitized mice treated with PBS.

Fig. 7

Comparison of Penh response in groups challenged with 20 mg/ml methacholine after 4 days of treatment. P = non-sensitized mice treated with PBS. HP = allergen-challenged mice treated with PBS, HR = allergen-challenged mice treated with 10 µg rfhSP-D (n = 4–8/group).

Fig. 8

Comparison of Penh response in groups challenged with 40 mg/ml methacholine on re-challenge with allergen given 4 days after the end of treatment. P = non-sensitized, treated with PBS. HP = allergen-challenged mice treated with PBS, HR = allergen-challenged mice treated with 10 µg rfhSP-D (n = 4–8/group).