Striking alterations in both collagen fibrils and basement membranes were revealed with the electron microscope in the lungs of rats exposed to subacute levels of nitrogen dioxide. Collagen fibrils underlying the terminal bronchiole in control rats increase slightly in size with age, and may appear stellate in cross section during old age. In marked contrast, young animals exposed to 17 ± 2 ppm for three months develop very large fibrils up to 15 times the normal diameter. The same response was observed in animals exposed to 2 ± 1 ppm for two or more years. The basement membrane under the epithelium of the terminal bronchiole also becomes greatly thickened. These alterations are seen after exposure to NO2 at subacute levels that endure neither edema nor significant destruction of cells but cause viable tissue to undergo metabolic alterations reflected by the changes described.
Stephens RJ, Freeman G, Evans MJ. Ultrastructural Changes in Connective Tissue in Lungs of Rats Exposed to NO2. Arch Intern Med. 1971;127(5):873-883. doi:10.1001/archinte.1971.00310170081011