Elastase-induced emphysema: retention of instilled proteinase in the rat.
Airway instillation of proteinases with the ability to degrade elastin has been used to produce disease in the rat analogous to human pulmonary emphysema. This study examined the retention, localization, and fate of endotracheally instilled elastase using 125Iodine labeled enzyme and immunoperoxidase histochemistry. Porcine pancreatic elastase labeled with 125I was detected in rat lungs through 96 h after instillation; over half of the label was still present after 7 h. Similar results were obtained when elastase was reacted with a specific, catalytic site inactivator prior to instillation. Trypsin and denatured elastase, however, were cleared much more rapidly from the lung (less than half of the label present after 30 min). When lungs were homogenized after instillation of active elastase, the soluble fraction contained elastase bound to rat alpha1-antitrypsin. In addition, a small amount of label (less than 10%) appeared bound to insoluble components for extended periods of time. Using immunoperoxidase histochemistry, it was found that exogenous elastase was rapidly contained with pulmonary alveolar macrophages, as well as associated with alveolar septums and other parenchymal structures. Similar results were obtained with elastase from both porcine pancreas and human neutrophils. These results suggest that exogenous elastase in the rat, and perhaps endogenous elastolytic enzymes in humans, may have several fates in the lungs: complex formation with endogenous inhibitors, containment within the macrophage, and/or association with connective tissue targets.
D000818:Animals; D004549:Elastin / Q000378:metabolism; D007124:Immunoenzyme Techniques; D007457:Iodine Radioisotopes; D008168:Lung / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D010196:Pancreatic Elastase / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000139:chemically induced* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014357:Trypsin / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000378:metabolism
D007457:Iodine Radioisotopes; D000515:alpha 1-Antitrypsin; D004549:Elastin; D010196:Pancreatic Elastase; D014357:Trypsin