Pulmonary elastic fiber degradation in paraquat toxicity. An electron microscopic immunohistochemical study.
To study the morphologic alterations of pulmonary elastic fibers in cynomolgus monkeys with paraquat toxicity, peroxidase- and ferritin-labeled antielastin antibodies were used for the light and electron microscopic localization of elastin. One week after paraquat, alveolitis, tissue damage and alveolar dilatation were present; elastic fibers were frayed and more diffusely and intensely stained than those of control animals. In the latter, staining was localized in peripheral regions of the amorphous components and, to a lesser extent, in some microfibrils of elastic fibers. At 3 to 4 weeks, diffuse staining was evident in damaged interstitial elastic fibers and in newly formed elastic fibers in areas of intraalveolar fibrosis. At 8 weeks, the interstitium contained many elastic fibers which showed staining only in peripheral regions of the amorphous components. These observations suggest that: 1) preembedding immunohistochemical staining for elastin is localized in peripheral regions of normal elastic fibers because the antielastin antibody can penetrate into mature and undamaged amorphous components only to a very limited extent; 2) in early stages of paraquat toxicity this staining is more diffuse and intense because elastase from inflammatory cells partially degrades the elastic fibers and permits greater penetration of the antibody into the amorphous materials; 3) in later stages the staining pattern returns to normal as inflammation subsides and elastic fibers are repaired; however, newly formed elastic fibers in areas of intraalveolar fibrosis stain diffusely, reflecting increased penetration of the antibody because of immaturity and incomplete cross-linking, and 4) degeneration of elastic fibers of alveolar walls in paraquat lung may lead to alveolar dilatation, which is associated with irregular fibrosis and constitutes one of the processes of pulmonary structural remodeling in paraquat lung.(ABSTRACT TRUNCATED AT 250 WORDS)
Fukuda
Y
Y
Pathology Branch, National Heart, Lung and Blood Institute, Bethesda, Maryland 20892.
Ferrans
V J
VJ
D000818:Animals; D004195:Disease Models, Animal; D004549:Elastin / Q000276:immunology / Q000502:physiology*; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000473:pathology*; D008252:Macaca fascicularis; D008854:Microscopy, Electron; D010269:Paraquat / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology
D004549:Elastin; D010269:Paraquat