Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Intranasal
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Allergens / immunology*
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Allergens / toxicity
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Animals
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Antibodies, Fungal / biosynthesis
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Antibodies, Fungal / immunology
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Antigens, Fungal / immunology*
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Antigens, Fungal / toxicity
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Antigens, Plant
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Aspergillosis, Allergic Bronchopulmonary / chemically induced
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Aspergillosis, Allergic Bronchopulmonary / drug therapy*
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Aspergillosis, Allergic Bronchopulmonary / pathology
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Aspergillus fumigatus / immunology*
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Bronchial Hyperreactivity / chemically induced
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Bronchial Hyperreactivity / drug therapy
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Drug Evaluation, Preclinical
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Eosinophilia / chemically induced
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Eosinophilia / drug therapy
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Female
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Fungal Proteins / immunology*
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Fungal Proteins / toxicity
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Humans
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Immunization
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Interferon-gamma / analysis
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Interleukin-12 / analysis
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Interleukin-4 / analysis
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Lung / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Peptide Fragments / administration & dosage
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Peptide Fragments / pharmacology
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Peptide Fragments / therapeutic use
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Plethysmography, Whole Body
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Pulmonary Surfactant-Associated Protein A / analysis
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Pulmonary Surfactant-Associated Protein A / pharmacology
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Pulmonary Surfactant-Associated Protein A / therapeutic use
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Pulmonary Surfactant-Associated Protein D / administration & dosage
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Pulmonary Surfactant-Associated Protein D / analysis
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Pulmonary Surfactant-Associated Protein D / chemistry
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Pulmonary Surfactant-Associated Protein D / pharmacology
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Pulmonary Surfactant-Associated Protein D / therapeutic use*
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Recombinant Fusion Proteins / administration & dosage
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Recombinant Fusion Proteins / pharmacology
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Recombinant Fusion Proteins / therapeutic use
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Species Specificity
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Spleen / chemistry
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Spleen / immunology
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Spleen / pathology
Substances
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ASPF1 protein, Aspergillus fumigatus
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Allergens
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Antibodies, Fungal
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Antigens, Fungal
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Antigens, Plant
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Fungal Proteins
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Peptide Fragments
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Pulmonary Surfactant-Associated Protein A
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Pulmonary Surfactant-Associated Protein D
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Recombinant Fusion Proteins
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Interleukin-12
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Interleukin-4
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Interferon-gamma