Differential modification of elastase-induced emphysema in hamsters by trypsin.
The administration of trypsin 24 h before, admixed with, or 24 h after administration of an emphysema-inducing dose of porcine pancreatic elastase (PPE) to hamsters resulted in significantly enhanced destruction of lung tissue as evidenced by mean linear intercept values 4 weeks post PPE. The coadministration of trypsin with a nonemphysema-inducing dose of PPE resulted in a significant destructive lung lesion. Administration of trypsin 24 h before or admixed with human leukocyte elastase (HLE) resulted in a lesion that was significantly reduced relative to that produced by administration of HLE alone. When trypsin was administered 24 h after HLE, no effect on the lesion was observed. In vitro, coincubation of trypsin with PPE resulted in a slight enhancement of rate of hydrolysis of elastin, while coincubation of trypsin with HLE resulted in a significant reduction of the rate of hydrolysis. These results suggest that interaction with other proteases may offer an additional physiological control mechanism to prevent inappropriate tissue destruction.
Williams
J C
JC
Department of Pharmacology, ICI Americas Inc., Wilmington, DE 19897.
Turpin
J A
JA
Townshend-Piala
P
P
D000818:Animals; D006224:Cricetinae; D004357:Drug Synergism; D004549:Elastin / Q000097:blood / Q000633:toxicity*; D006801:Humans; D006868:Hydrolysis; D007962:Leukocytes / Q000201:enzymology; D008647:Mesocricetus; D010179:Pancreas / Q000201:enzymology; D010196:Pancreatic Elastase; D011656:Pulmonary Emphysema / Q000139:chemically induced*; D013552:Swine; D014357:Trypsin / Q000633:toxicity*
D004549:Elastin; D010196:Pancreatic Elastase; D014357:Trypsin