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Clin Exp Allergy ; 36(7): 930-40, 2006 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-16839409

RESUMEN

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.


Asunto(s)
Alérgenos/inmunología , Aspergillus fumigatus/inmunología , Asma/prevención & control , Proteína D Asociada a Surfactante Pulmonar/uso terapéutico , Administración por Inhalación , Animales , Antígenos Fúngicos/inmunología , Asma/inmunología , Asma/metabolismo , Hiperreactividad Bronquial/inmunología , Hiperreactividad Bronquial/metabolismo , Hiperreactividad Bronquial/prevención & control , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Quimiocina CCL11 , Quimiocinas CC/metabolismo , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Eosinofilia/prevención & control , Femenino , Liberación de Histamina/efectos de los fármacos , Inmunoglobulina E/sangre , Interleucina-5/metabolismo , Pulmón/metabolismo , Rendimiento Pulmonar , Ratones , Ratones Endogámicos BALB C , Proteína D Asociada a Surfactante Pulmonar/farmacocinética , Proteínas Recombinantes/uso terapéutico
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