This approach will see increasing use in the future. It has the attraction that probes can be synthesized to detect specific patterns of alternative splicing, but the limitation that mRNa may not always be translated.
In the adult respiratory distress syndrome (ARDS), repair processes are set in motion. In fatal cases, the collagen content of the lung increases during the second week of disease. The sites of connective-tissue deposition are variable and complex. Much connective tissue deposition is within air spaces. The hyaline membranes of the acute phase of ARDS line alveolar ducts, and the most characteristic localization of collagen synthesis during repair in ARDS also follows alveolar ducts (Fig 1, top), permitting the inference that organization of hyaline membranes is taking place. However, in individual cases, collagen synthesis can be detected in the alveolar interstitium, in the fibroblasts of the perilobular septa, and in the smooth muscle cells of arteries as well as within air spaces.
In several forms of relatively acute fibrosing lung disease, fibroblasts deposit connective tissue in respiratory bronchioles and alveolar ducts in the form of polypoid buds of fibroblasts and extracellular matrix called Masson bodies (Table 1).
Figure 1. Top, Reparative phase of diffuse alveolar damage. Distribution of matrix containing active fibroblasts (staining brown for procollagen) follows alveolar ducts in a distribution similar to that of hyaline membranes in acute diffuse alveolar damage (im-munoperoxidase stain for procollagen type I (brown) and immuno-glucose oxidase for type IV collagen (purple) x 230). Center, Masson bodies of bronchiolitis obliterans with organizing pneumonia. Fibroblasts with procollagen (brown) are within air spaces. Interstitium delineated by basal lamina (blue) is minimally thickened (immunoperoxidase for procollagen type I and immunoalkaline phosphatase for type IV collagen X 230). Bottom, Usual interstitial pneumonia (UIP). Two foci of active collagen synthesis (arwws) are illustrated in a badly distorted lung. Smudgy, discontinuous remnants of basal lamina are present beneath the fibroblasts, but none covers their surface, indicating that they are located within the lumen of an air space (immunoperoxidase for procollagen type I and glucose oxidase for type IV collagen x 230).
Table 1—Some Conditions Causing Air-Space Organization by Masson Bodies
|Organizing infectious pneumonia|
|Diffuse alveolar damage in ARDS|
|Idiopathic bronchiolitis obliterans with organizing pneumonia|
|Drug and chemical pneumonitis|