152 Chapter 12 Pathophysiology of elastin Alveolar myofibroblasts are located underneath the alveolar epithelium, and are defined by expression of α-smooth muscle actin and the production of elastin and collagen267. In alveolar development, deposition of elastin is an essential process for septation. Elastin allows alveoli to stretch during inhalation268. After birth, elastin forms a matrix, serving as a scaffold on which alveolar myofibroblasts adhere and mark the sites of secondary septa267. Cyclic mechanical stretch is important to maintain the alveolar myofibroblast state269. In a model system of pulmonary fibrosis, the mechanical stretch is reduced and myofibroblast differentiation is increased269. Moreover, pre-existing elastin has been shown to induce an increase in extracellular elastin production by myofibroblasts. This explains the focal increase in the amount of elastin in areas with pre-existing elastin. As well as the increased expression of elastin, expression levels of the α1 chain of type V collagen and tenascin C are increased269. In chronic obstructive pulmonary disease, abnormal fibulin-5 metabolism is suggested to play a role in disturbed elastogenesis270. In pleuroparenchymal fibroelastosis, the combination of increased numbers of subepithelial myofibroblasts and increased amounts of elastin in continuous sheets was demonstrated in areas with mild non-specific interstitial pneumonia271. This distribution of elastic fibers is similar to that seen in some cases of AIS and lepidic adenocarcinoma. These findings suggest that: (i) in AIS and non-specific interstitial pneumonia, an interaction between epithelial cells, extracellular matrix components and subepithelial myofibroblasts leads to increased elastin production; and (ii) the light-microscopic demonstration of continuous elastic fibers (corresponding to ‘elastin sheets’ in the third dimension) cannot be used as a criterion for invasion. In pulmonary adenocarcinomas, Matsubara et al.272 emphasized two locations of myofibroblasts, i.e. the above-mentioned alveolar subepithelial myofibroblasts and the stromal myofibroblasts, often in areas of central fibroelastosis. The subepithelial myofibroblast pattern is associated with a favorable prognosis273. Terminology of elastin degradation In 2000, Fukushima et al. used the term ‘degradation of elastin’ in an electronmicroscopic study for the examination of pulmonary carcinomas. On ultrastructural examination (high magnification), some thick elastic fibers showed vacuolar changes and electron-dense granular deposits274. These changes were called ‘degradation’ of elastic fibers. Thus, the term ‘elastin degradation’, in this sense, constitutes an electronmicroscopic definition of individual fibers, referring to features that are not readily recognisable with light microscopy. In pulmonary adenocarcinomas, Eto et al273. performed a light-microscopic histological image analysis study using elastin stains, and noticed, in the central fibrotic ‘invasive’ part of peripheral adenocarcinomas, a disrupted pattern of the elastotic framework related to invasion and a poor prognosis. It is of note that they described, in the periphery of the tumour, a thin-walled elastic framework similar to normal alveolar walls. Fukushima et al.274 compared elastin in non-malignant peripheral lung with that
RkJQdWJsaXNoZXIy MTk4NDMw