Pulmonary alveolar proteinosis in SCID mice

Pulmonary alveolar proteinosis (PAP) is an uncommon disorder of unknown origin in which the alveoli are filled with lipoproteinaceous material, including surfactant. We have characterized a spontaneously occurring lesion in the lungs of CB.17 scid/scid mice which resembles PAP in humans. Lungs from 45 severe combined immunodeficient (SCID) mice were evaluated by light and electron microscopy and immunohistochemistry. Lung lavage fluid was evaluated biochemically and for the presence of surfactant protein A (SP-A) and B (SP-B) by enzyme-linked immunosorbent assay and Western blot. Light microscopy showed varying amounts of a homogeneous to granular proteinaceous material in alveolar spaces. This material was eosinophilic by hematoxylin and eosin stain and was periodic acid-Schiff (PAS) positive. Ultrastructurally, the material was predominantly homogeneous with areas of a lamellated pattern that resembled surfactant. Biochemical analysis revealed 2.7- and 3.6-fold increases in the surfactant-associated phospholipids phosphatidylcholine and disaturated phosphatidylcholine respectively, when affected SCID mice were compared with control mice. Immunohistochemical staining of lung tissue and Western blot and enzyme-linked immunosorbent assay of lavage fluid showed marked increases in SP-A and SP-B in comparison with controls. These results suggest that SCID mice have a defect in surfactant homeostasis that resembles PAP in humans and may serve as an animal model in further elucidating the pathogenesis of this disease.