Ultrastructural analysis of pulmonary alveolar proteinosis induced by methylnaphthalene in mice.

Pulmonary alveolar proteinosis was induced at a 100% incidence in B6C3F1 female mice by twice weekly painting the back skin with methylnaphthalene for 30 weeks to give a total dose of 7.14 g/kg b.wt. Semithin sections were used for defining areas of type II pneumocyte hyperplasia and hypertrophy and associated proteinosis. Ultrastructurally, alveolar spaces were found to be filled with numerous myelinoid structures resembling the lamellar bodies of type II pneumocytes. Mononucleated giant cells (balloon cells, BC) containing numerous myelinoid structures, lipid droplets and many electron dense amorphous ascicular crystals were closely associated with this extracellular membranous material. Stacks of elastic fibers stained with tannic acid and bundles of collagen fibers were loose and discontinuous in the interstitium of affected areas. The following pathogenesis is hypothesized: type II pneumocytes produce increased amounts of lamellar bodies due to their hyperplasia and hypertrophy and develop to form BC which liberate numerous myelinoid structures on their rupture. Epidermal absorption of methylnaphthalene is an efficient reliable method of induction of this internal disease.