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

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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.

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Gleb V. Sychugov

South Ural State Medical University affiliated, Ministry of Health of the Russian Federation

Email: docsgv@yandex.ru
ORCID iD: 0000-0003-3251-6944
Russian Federation, Chelyabinsk

Tamara V. Azizova

Southern Urals Biophysics Institute affiliate, Federal Medical Biological Agency

Author for correspondence.
Email: clinic@subi.su
ORCID iD: 0000-0001-6954-2674
Russian Federation, Ozyorsk

Sergey V. Osovets

Southern Urals Biophysics Institute affiliate, Federal Medical Biological Agency

Email: osovets1@yandex.ru
ORCID iD: 0000-0002-6180-2061
Russian Federation, Ozyorsk

Evgeniy L. Kazachkov

South Ural State Medical University affiliated, Ministry of Health of the Russian Federation

Email: doctorkel@yandex.ru
ORCID iD: 0000-0002-4512-3421
Russian Federation, Chelyabinsk

Evgeniya S. Grigoryeva

Southern Urals Biophysics Institute affiliate, Federal Medical Biological Agency

Email: grig@subi.su
ORCID iD: 0000-0003-1806-9922
Russian Federation, Ozyorsk

Alexsander G. Sychugov

South Ural State Medical University affiliated, Ministry of Health of the Russian Federation

Email: docsgv@yandex.ru
ORCID iD: 0009-0004-4803-1022
Russian Federation, Chelyabinsk

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2. Fig. 1. The use of pseudocolor masks above images highlighting MMP-9 expression in vessel endothelium and lung fiber components of the lung stroma for quantification of metalloproteinase content in a lung tissue section.

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3. Fig. 2. Expression of collagens type I, IV and V in LF and non-LF specimens. Immunohistochemistry with antibodies against Collagen type I, Collagen type IV, Collagen type V, polymer test-system. Magnification ×50. Scale 500 μm. LF and ППФ denotes plutonium-induced lung fibrosis, non-LF denote lung fibrosis of a different origin, ГС denotes control (no pulmonary pathology).

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4. Fig. 3. Expression of matrix metalloproteinases and their tissue inhibitors in LFR and non-LFR. Immunohistochemical method with antibodies against MMP-2, MMP-9, TIMP-1, TIMP-2, polymer test system. Magnification ×400. Marker 50 µm. LFR and PPF — radiation pulmonary fibrosis, non-LFR — nonradiative pulmonary fibrosis, GS — comparison group (non-LFR).

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