Intranasal delivery of a truncated recombinant human SP-D is effective at down-regulating allergic hypersensitivity in mice sensitized to allergens of Aspergillus fumigatus

Clin Exp Immunol. 2002 Oct;130(1):19-24. doi: 10.1046/j.1365-2249.2002.01968.x.

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

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Allergens / immunology*
  • Allergens / toxicity
  • Animals
  • Antibodies, Fungal / biosynthesis
  • Antibodies, Fungal / immunology
  • Antigens, Fungal / immunology*
  • Antigens, Fungal / toxicity
  • Antigens, Plant
  • Aspergillosis, Allergic Bronchopulmonary / chemically induced
  • Aspergillosis, Allergic Bronchopulmonary / drug therapy*
  • Aspergillosis, Allergic Bronchopulmonary / pathology
  • Aspergillus fumigatus / immunology*
  • Bronchial Hyperreactivity / chemically induced
  • Bronchial Hyperreactivity / drug therapy
  • Drug Evaluation, Preclinical
  • Eosinophilia / chemically induced
  • Eosinophilia / drug therapy
  • Female
  • Fungal Proteins / immunology*
  • Fungal Proteins / toxicity
  • Humans
  • Immunization
  • Interferon-gamma / analysis
  • Interleukin-12 / analysis
  • Interleukin-4 / analysis
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / pharmacology
  • Peptide Fragments / therapeutic use
  • Plethysmography, Whole Body
  • Pulmonary Surfactant-Associated Protein A / analysis
  • Pulmonary Surfactant-Associated Protein A / pharmacology
  • Pulmonary Surfactant-Associated Protein A / therapeutic use
  • Pulmonary Surfactant-Associated Protein D / administration & dosage
  • Pulmonary Surfactant-Associated Protein D / analysis
  • Pulmonary Surfactant-Associated Protein D / chemistry
  • Pulmonary Surfactant-Associated Protein D / pharmacology
  • Pulmonary Surfactant-Associated Protein D / therapeutic use*
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / pharmacology
  • Recombinant Fusion Proteins / therapeutic use
  • Species Specificity
  • Spleen / chemistry
  • Spleen / immunology
  • Spleen / pathology

Substances

  • ASPF1 protein, Aspergillus fumigatus
  • Allergens
  • Antibodies, Fungal
  • Antigens, Fungal
  • Antigens, Plant
  • Fungal Proteins
  • Peptide Fragments
  • Pulmonary Surfactant-Associated Protein A
  • Pulmonary Surfactant-Associated Protein D
  • Recombinant Fusion Proteins
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma