Elastase-induced emphysema: retention of instilled proteinase in the rat

Journal Article · Mon Nov 01 04:00:00 EST 1982 · Am. Rev. Respir. Dis.; (United States)

OSTI ID:6120729

Sandhaus, R A; Janoff, A

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 /sup 125/I labeled enzyme and immunoperoxidase histochemistry. Porcine pancreatic elastase labeled with /sup 125/I 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.

• Research Organization: Department of Pathology, State University of New York at Stony Brook
• OSTI ID: 6120729
• Journal Information: Am. Rev. Respir. Dis.; (United States), Journal Name: Am. Rev. Respir. Dis.; (United States) Vol. 126:5; ISSN ARRDA
• Country of Publication: United States
• Language: English

Related Subjects

550901* -- Pathology-- Tracer Techniques
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59 BASIC BIOLOGICAL SCIENCES
ANIMAL TISSUES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL LOCALIZATION
BIOLOGICAL MODELS
BODY
CONNECTIVE TISSUE
DAYS LIVING RADIOISOTOPES
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
EMPHYSEMA
ENZYME ACTIVITY
ENZYMES
ETIOLOGY
HYDROLASES
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
NUCLEI
ODD-EVEN NUCLEI
PEPTIDE HYDROLASES
RADIOISOTOPES
RATS
RESPIRATORY SYSTEM DISEASES
RETENTION
RODENTS
TISSUES
TRACER TECHNIQUES
VERTEBRATES