Intranasal delivery of a truncated recombinant human SP-D is effective at down-regulating allergic hypersensitivity in mice sensitized to allergens of Aspergillus fumigatus.
C57BL/6 mice were sensitized to Aspergillus fumigatus 1-week culture filtrate, which is rich in the non-glycosylated allergen Asp f1, a major allergen in allergic bronchopulmonary aspergillosis (ABPA). A comparison of the effect of treatment of allergen challenged mice by intranasal administration of a 60-kDa truncated recombinant form of human SP-D (rfhSP-D) or recombinant full length SP-A (rhSP-A) was undertaken. Treatment with rfhSP-D produced significant reduction in IgE, IgG1 and peripheral blood eosinophilia and treatment with rfhSP-D, but not rhSP-A resulted in a significant reduction in airway hyperresponsiveness as measured by whole body plethysmography. Lung histology revealed less peribronchial lymphocytic infiltration in mice treated with rfhSP-D. Intracellular cytokine staining of spleen homogenates showed increases in IL-12 and IFN-gamma and decrease in IL-4. The level of endogenous mouse SP-D was elevated sixfold in the lungs of sensitized mice and was not affected by treatment with rfhSP-D. Taken with our previous studies, with a BALB/c mouse model of ABPA using a 3-week A. fumigatus culture filtrate, the present results show that rfhSP-D can suppress the development of allergic symptoms in sensitized mice independent of genetic background and using a different preparation of A. fumigatus allergens.
Strong
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Medical Research Council Immunochemistry Unit, University of Oxford, UK. peter.strong@bioch.ox.ac.uk
Reid
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Clark
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D000281:Administration, Intranasal; D000485:Allergens / Q000276:immunology* / Q000633:toxicity; D000818:Animals; D000908:Antibodies, Fungal / Q000096:biosynthesis / Q000276:immunology; D000946:Antigens, Fungal / Q000276:immunology* / Q000633:toxicity; D052179:Antigens, Plant; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D001232:Aspergillus fumigatus / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000188:drug therapy; D004353:Drug Evaluation, Preclinical; D004802:Eosinophilia / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D005656:Fungal Proteins / Q000276:immunology* / Q000633:toxicity; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D015847:Interleukin-4 / Q000032:analysis; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010993:Plethysmography, Whole Body; D037662:Pulmonary Surfactant-Associated Protein A / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use; D037663:Pulmonary Surfactant-Associated Protein D / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013045:Species Specificity; D013154:Spleen / Q000737:chemistry / Q000276:immunology / Q000473:pathology
C081947:ASPF1 protein, Aspergillus fumigatus; D000485:Allergens; D000908:Antibodies, Fungal; D000946:Antigens, Fungal; D052179:Antigens, Plant; D005656:Fungal Proteins; D010446:Peptide Fragments; D037662:Pulmonary Surfactant-Associated Protein A; D037663:Pulmonary Surfactant-Associated Protein D; D011993:Recombinant Fusion Proteins; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma