Ultrastructure: In the toluidine blue-stained, plastic-embedded lung prepared for electron microscopy, the interstitium of the pulmonary parenchyma was markedly thickened with abundant collagen. In the areas of type II pneumocyte hyperplasia and differentiation, the individual pneumocytes contained many cytoplasmic, variably sized dark inclusions; similar bodies were not seen in normal feline lung (Fig 5, top left, A, and top right, B). By ultrastructure, the type II pneumocytes of normal cats are as described for other species, with surface microvilli and lamellar bodies with stacks of phospholipid membranes (Fig 5, middle left, C). The type II pneumocytes in the IPF cat lung were markedly enlarged (Fig 5, middle right, D), with numerous large condensed lamellar body-like structures (Fig 5, bottom left, E, and bottom right, F). These cells were often free within the lumen of the airspace. Abnormal lamellar bodies were seen within alveolar macrophages as well as occasionally free within the interstitium of the fibrotic lungs. Similar type II pneumocytes were found distant from the foci of remodeling, in the more normal lung parenchyma (data not shown). fully
IPF is a poorly understood chronic respiratory disease of humans. Complicating advancements in understanding the pathogenesis of the disease and development of therapies is the lack of animal models of the disease that follow the progressive clinical course, and which develop the persistent, progressive lung fibrosis characteristic of the disease. Identification of new animal models of IPF is a stated priority of the National Heart, Lung, and Blood Institute of the National Institutes of Health.2 An ideal animal model of IPF should recapitulate the complex lung morphology and clinical progression of the human disease; descriptive features of both the lung morphology and clinical disease should emphasize the persistent, progressive fibrosis characteristic of IPF.
Figure 5. Feline IPF type II pneumocyte morphology, showing toluidine-blue stained, plastic-embedded normal (top left, A) and feline IPF (top right, B) lung. Type II pneumocytes in feline IPF contain dense cytoplasmic inclusions that are not visible in normal type II cells (arrowheads). Also shown are ultrastructure of normal (middle left, C) and feline IPF (middle right, D) type II pneumocytes. In feline IPF, the type II cells are hypertrophied and contain many dense cytoplasmic, lamellar body-like structures. Also shown are detailed ultrastructure of normal feline lamellar bodies (bottom left, E) and abnormal lamellar body-like inclusions in feline IPF (bottom right, F). Bars in top left, A, and top right, B indicate 50 |j,m; middle left, C, and middle right, D are original X 5,700; bottom left, E, and bottom right, F are original X 25,000.