The effect of lysozyme on elastase-mediated injury.
Previous studies by this laboratory demonstrated that lysozyme is increased in human pulmonary emphysema, and that it preferentially binds to elastic fibers, which undergo degradation in this disease. In the current investigation, the relationship between lysozyme and elastic fiber injury was further examined, both in vitro and in vivo. The effect of exogenously administered egg-white lysozyme on pancreatic elastase-induced injury was determined using a biosynthetically radiolabeled extracellular matrix preparation mainly composed of elastic fibers. Although matrix treated with lysozyme showed attachment of the protein to elastic fibers, there was no significant increase in elastolysis compared with untreated controls following exposure to either 1 microg/ml or 100 ng/ml of pancreatic elastase. However, lysozyme did impair the ability of hyaluronan (HA) to prevent elastase injury to elastic fibers. Matrix samples sequentially treated with lysozyme and HA, then incubated with 1 microg/ml or 100 ng/ml of pancreatic elastase, showed significantly increased elastolysis compared with those treated with HA alone. Since HA is closely associated with elastic fibers in vivo, the ability of lysozyme to enhance elastolysis was further tested in an animal model of emphysema induced by intratracheal administration of porcine pancreatic elastase. Animals exposed to aerosolized lysozyme prior to elastase administration showed significantly increased airspace enlargement. The mean linear intercept of the lysozyme-treated animals was 123 microm compared with 75 microm for controls receiving aerosolized water (P < 0.0001). These findings suggest that lysozyme may not be an innocuous component of the inflammatory response associated with pulmonary emphysema, but may actually play a role in the pathogenesis of the disease.
Cantor
Jerome O
JO
St. Luke's-Roosevelt Hospital Center, New York, New York, USA. JOCANTOR@pol.net
Shteyngart
Bronislava
B
Cerreta
Joseph M
JM
Turino
Gerard M
GM
D000818:Animals; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D009113:Muramidase / Q000378:metabolism* / Q000494:pharmacology; D010196:Pancreatic Elastase / Q000633:toxicity*; D011656:Pulmonary Emphysema / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D051381:Rats
D006820:Hyaluronic Acid; D009113:Muramidase; D010196:Pancreatic Elastase