Surfactant protein d for the prevention and diagnosis of...

A - Human Necessities – 61 – K

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A61K 48/00 (2006.01) A61K 31/7088 (2006.01) A61K 38/17 (2006.01) A61P 11/00 (2006.01) A61P 37/08 (2006.01) C07K 14/785 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2463091

Surfactant protein D (SP-D) is a 43-kDa member of the collectin family of collagenous lectin domain-containing proteins that is expressed in epithelial cells of the lung. The SP-D gene was targeted by homologous recombination in embryonic stem cells that were used to produce SP-D (-/-) mice. The SP-D (-/-) deficiency caused inflammation, increased oxidant production by isolated alveolar macrophages, abnormal surfactant structure and levels, and decreased SP-A expression. Therefore, disclosed is the SP-D (-/-) mouse as an excellent model for emphysema. Also included are models for testing emphysema therapies in the mouse model, methods for using SP-D protein or DNA as a treatment for emphysema and pulmonary infections, and diagnosis.

L'invention concerne la protéine tensioactive D (SP-D), un élément à 43-kDa de la famille des collectines des protéines du collagène contenant un domaine de lectine, exprimé dans les cellules épithéliales des poumons. Le gène SP-D a été ciblé par recombinaison homologue dans des cellules souches embryonnaires utilisées pour produire des souris SP-D (-/-). La carence SP-D (-/-) a provoqué une inflammation, une production accrue d'oxydants par des macrophages alvéolaires isolés, une structure et des niveaux de tensioactifs anormaux et une expression de SP-A réduites. L'invention concerne donc la souris SP-D (-/-) en tant qu'excellent modèle pour l'emphysème. Elle concerne également des modèles permettant de tester des traitements de l'emphysème dans le modèle murin, des procédés d'utilisation de la protéine ou de l'ADN SP-D pour le traitement et le diagnostic de l'emphysème et des infections pulmonaires.

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