Pathomorphological Features of Lung Fibrosis in Individuals Occupationally Exposed to Alpha Radiation

Abstract

The aim of this study was to search for the specific morphological features of radiation-induced lung fibrosis compared to pulmonary fibrosis of another origin, using biological specimens of lung tissue collected from workers internally exposed to alpha radiation. The morphological features of lung fibrosis were defined using biological specimens of lung tissue that had been collected during autopsy examinations from 56 workers diagnosed with plutonium-induced lung fibrosis during life, from 34 workers with lung fibrosis of another origin (due to chronic inflammatory lung diseases) and from 35 workers without clinical pulmonary pathology (controls). The total lung-absorbed dose of gamma radiation from external exposure did not significantly differ among the studied groups, and the total lung-absorbed dose of alpha radiation from internal exposure was significantly higher in workers with plutonium-induced lung fibrosis. To investigate the extracellular matrix components, mono- and polyclonal labeled antibodies against type I, IV, and V collagens were used. In addition, to evaluate the system of extracellular matrix metabolism regulation, the antibodies against matrix metalloproteinases MMP-2, MMP-9, tissue inhibitors of matrix metalloproteinases TIMP-1 and TIMP-2 were used. The study revealed qualitative and quantitative morphological peculiarities of plutonium-induced lung fibrosis compared to lung fibrosis of another origin. This allows us to conclude that plutonium-induced lung fibrosis is a specific type of lung fibrosis, which is characterized with specific location and architectonics of fibrosis foci within the lung, and with changes in levels of collagen, elastic and reticular fibers in the pulmonary stroma. The analysis demonstrated that hyperproduction of type V collagen plays a key role in the development of plutonium-induced lung fibrosis. In addition, the imbalance between the expression of MMPs and their inhibitors plays an important role in the development of lung fibrosis.