PULMONARY ALVEOLAR PROTEINOSIS IN SCID MICE

Pulmonary alveolar proteinosis (PAP) is an uncommon disorder of unknow n origin in which the alveoli are filled with lipoproteinaceous materi al, including surfactant, We have characterized a spontaneously occurr ing lesion in the lungs of CB.17 scid/scid mice which resembles PAP in humans, Lungs from 45 severe combined immunodeficient (SCID) mice wer e 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 immunosorbe nt assay and Western blot, Light microscopy showed varying amounts of a homogeneous to granular proteinaceous material in alveolar spaces. T his material was eosinophilic by hematoxylin and eosin stain and was p eriodic acid-Schiff (PAS) positive. Ultrastructurally, the material wa s predominantly homogeneous with areas of a lamellated pattern that re sembled surfactant. Biochemical analysis revealed 2.7- and 3.6-fold in creases 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 wi th controls. These results suggest that SCID mice have a defect in sur factant homeostasis that resembles PAP in humans and may serve as an a nimal model in further elucidating the pathogenesis of this disease.