Surfactant protein D inhibits early airway response in Aspergillus fumigatus-sensitized mice

Clin Exp Allergy. 2006 Jul;36(7):930-40. doi: 10.1111/j.1365-2222.2006.02524.x.

Abstract

Background: The surfactant protein SP-D has been reported to reduce bronchial hyper-responsiveness, blood eosinophilia, and T-helper type 2 cytokines in models of allergic asthma. However, little is known about the functional effect of SP-D on the early airway response upon allergen inhalation, which is an important feature of this disease.

Objective: We investigated whether SP-D is able to reduce the immediate allergen-induced mediator release and the early bronchial obstruction in addition to its effects on airway inflammation and bronchial hyperresponsiveness in an Aspergillus fumigatus mouse asthma model.

Methods: A. fumigatus-sensitized mice were treated with a recombinant fragment of human SP-D or placebo. Lung functions were measured in orotracheally intubated, spontaneously breathing animals using body plethysmography. In addition, passively sensitized precision-cut lung slices (PCLS) were used to determine the effect of SP-D on allergen-induced histamine release.

Results: SP-D inhibited the allergen-induced early airway response and reduced airway hyperresponsiveness compared with placebo. Eosinophilia in bronchoalveolar lavage and lung tissue was reduced after SP-D treatment, possibly by reducing eotaxin levels in the lung. Furthermore, SP-D treatment reduced the allergen-induced histamine release from PCLS.

Conclusion: These data suggest that SP-D not only reduces allergen-induced eosinophilic inflammation and airway hyperresponsiveness but also provides protection against early airway obstruction by inhibition of early mediator release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Allergens / immunology*
  • Animals
  • Antigens, Fungal / immunology
  • Aspergillus fumigatus / immunology*
  • Asthma / immunology
  • Asthma / metabolism
  • Asthma / prevention & control*
  • Bronchial Hyperreactivity / immunology
  • Bronchial Hyperreactivity / metabolism
  • Bronchial Hyperreactivity / prevention & control
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Chemokine CCL11
  • Chemokines, CC / metabolism
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Eosinophilia / prevention & control
  • Female
  • Histamine Release / drug effects
  • Immunoglobulin E / blood
  • Interleukin-5 / metabolism
  • Lung / metabolism
  • Lung Compliance
  • Mice
  • Mice, Inbred BALB C
  • Pulmonary Surfactant-Associated Protein D / pharmacokinetics
  • Pulmonary Surfactant-Associated Protein D / therapeutic use*
  • Recombinant Proteins / therapeutic use

Substances

  • Allergens
  • Antigens, Fungal
  • CCL11 protein, human
  • Ccl11 protein, mouse
  • Chemokine CCL11
  • Chemokines, CC
  • Interleukin-5
  • Pulmonary Surfactant-Associated Protein D
  • Recombinant Proteins
  • Immunoglobulin E