Defenses of the hamster lung against human neutrophil and porcine pancreatic elastase.
Instillation of human neutrophil elastase (HNE) into hamster lungs produces milder emphysema but more pulmonary hemorrhage than an equivalent amount of porcine pancreatic elastase (PPE), whether equivalence is determined by elastolytic units or moles. We undertook a study of the mechanisms of these differences. 125I-HNE or 3H-PPE were instilled intratracheally into hamsters. The partitioning of radioactivity between bronchoalveolar lavage fluid (BAL) and lung tissue was similar for HNE and PPE as were the half-lives, 45 and 51 min, respectively, for uncomplexed, enzymatically active HNE and PPE. In BAL there was preferential binding and inactivation of HNE by the hamsters' alpha-1-protease inhibitor (a-1-PI) whereas PPE was preferentially bound by alpha-2-macroglobulin (a-2-M). This was also observed in vitro when HNE and PPE were incubated with plasma from untreated hamsters. Nevertheless, when the sum of the elastase binding capacity of a-1-PI and a-2-M was considered, hamster plasma had similar binding capacities for HNE and PPE. It is known that the enzymatic activity of elastases is inhibited by formation of a stable complex with a-1-PI. On the other hand, elastases bound to a-2-M are protected against a-1-PI inhibition but can free themselves by proteolysis and exhibit elastolytic activity. Preferential inactivation of HNE by a-1-PI may be one mechanism that accounts for the lesser emphysema-inducing potency of HNE than of PPE.
Stone
P J
PJ
Department of Biochemistry, Boston University School of Medicine, Mass.
Lucey
E C
EC
Calore
J D
JD
McMahon
M P
MP
Snider
G L
GL
Franzblau
C
C
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000201:enzymology / Q000378:metabolism; D006224:Cricetinae; D004547:Elastic Tissue / Q000187:drug effects; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000503:physiopathology*; D008171:Lung Diseases / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009504:Neutrophils / Q000201:enzymology*; D010196:Pancreatic Elastase / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011480:Protease Inhibitors / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000378:metabolism*; D013552:Swine; D000515:alpha 1-Antitrypsin / Q000378:metabolism; D000511:alpha-Macroglobulins / Q000378:metabolism
D011480:Protease Inhibitors; D000515:alpha 1-Antitrypsin; D000511:alpha-Macroglobulins; D010196:Pancreatic Elastase