| Type I and III procollagen propeptides in sarcoidosis, fibrosing alveolitis and asbestos-related lung diseases | ||
|---|---|---|
| Prev | Chapter 2. Review of the literature | Next |
Mature collagen I is located in alveolar septa, whereas collagen III is mainly occurs in capillary walls and aggregates of collagen in healthy normal lung. Collagen IV and V are located in alveolar and capillary basement membrane. (Madri & Furthmayr 1980). Collagen I has also been detected in pleural, peribronchial and perivascular connective tissue as well as in bronchial mucosa and subintima. Collagen III is expressed mainly in the latter two locations. (Bateman et al. 1981). Immunoreactivity of procollagen I carboxyterminal propeptide has not been detected in normal lung specimens (McDonald et al. 1986, Roman et al. 1995).
Sarcoidosis granulomas have been shown to include interstitial collagens I and III. In the early stage of the disease, both collagens have been detected peripherally, whereas in mature and late stages they are also seen around and within granulomas (Peyrol et al. 1986, Roman et al.1995). PICP immunoreactivity has been shown to be distributed within multinucleated giant cells, macrophages and surrounding fibroblasts (Roman et al. 1995). Granulomas from tuberculosis and sarcoidosis skin biopsy specimens have been found to contain PICP positive cells showing fibroblast morphology and being scattered throughout the granuloma core. Accentuated staining for the extracellular matrix has been seen both in granulomas and in the peri-granulomatous regions. (Marshall et al. 1996).
The mean percentage of type I collagen appears to be higher than that of type III collagen in autopsy samples from patients who died of fibrosing alveolitis as compared to open lung biopsies and controls (Kirk et al. 1984). In fibrotic lung, collagen I has been shown to be markedly increased throughout the thickened septa, whereas collagen III is absent from the septa, although detectable in vascular structures (Madri & Furthmayr 1980). Collagen I forms an irregular pattern in all zones of fibrosis, whereas collagen III is less intensively stained in some areas (Takiya et al. 1983). Bateman et al. (1983) has shown that collagen I predominates at all sites of fibrosis, and in areas where the fibre bundles are closely packed, collagen I stains are weaker and collagen III is not detectable. Some fibrosis patients show collagen III at subepithelial sites or in loosely arranged fibrils between densely packed collagen I fibres in alveolar walls. These collagen III-positive patients deteriorate in follow-up. (Bateman et al 1983).
Collagen I mRNA has been detected in acute interstitial pneumonitis of Hamman-Rich type, bleomycin-induced fibrosis, bronchitis obliternas organising pneumonia and fibrosing alveolitis. Collagen I protein can only be detected in fibrosing alveolitis, whereas both collagen III and IV and their mRNA have been observed in all of the abovementioned disorders. (Specks et al. 1995).
In biopsies obtained from patients with active fibrosis, anti-PICP antibodies stained intensely both interstitial and alveolar fibroblasts, whereas patients with quiescent disease show no immunoreactivity (McDonald et al. 1986). Kuhn et al. (1989) demonstrated that only 13/22 patients with fibrosing alveolitis show collagen-synthesising fibroblasts with PICP positivity, and the extent of staining varied within 1-20%. Immunoreactive fibroblasts form subepithelial clusters (fibroblastic foci) near the air-tissue interface, and the cells closer to the air-tissue interface are larger and more intensively stained than the deeper cells. The cells comprising these clusters are spindle-shaped and usually arrayed parallel to one another. Active synthesis of type I procollagen in these foci has been shown by the myofibroblasts, which are α-smooth muscle actin-positive fibroblast-like cells with contractile filament-laden stroma. (Kuhn & McDonald 1991).
Procollagen I aminoterminal propeptide has been detected in myofibroblasts of fibroblast foci with relatively little mature collagen compared to other areas (Bensadoun et al. 1996).