Am. J. Respir. Cell Mol. Biol., Vol 11, No. 1, Jul 1994, 103-107.
Inhibition of neutrophil elastase by mucus glycoprotein
C Nadziejko and I Finkelstein
Institute of Environmental Medicine, New York University Medical Center, Tuxedo 10987.
A number of structurally diverse polyanions have been found to inhibit
human leukocyte elastase (HLE) activity. The purpose of this study was to
examine the effects of mucus glycoprotein (mucin), one of the most
plentiful high molecular weight polyanions in the respiratory tracts, on
HLE activity. Human airway mucin and bovine submaxillary mucin at
concentrations of 0.4 to 2.8 mg/ml both markedly inhibited the elastolytic
activity of 50 nM HLE, with maximum inhibition approaching 90%. The degree
of inhibition was the same regardless of whether the mucin, elastase, and
elastin were simultaneously combined or whether the mucin was added to
elastase 20 min prior to adding elastin, indicating that mucin is a
rapid-acting inhibitor. The shape of the inhibition curve resembled that of
curves obtained using heparin and HLE. Mucin had little inhibitory effect
on pancreatic elastase, which is structurally related to but less cationic
than HLE. The inhibition of HLE by mucin was blocked by 1 M NaCl. Removal
of sulfate esters by acid-catalyzed solvolysis markedly reduced the
inhibitory effect of bovine submaxillary mucin. These results indicate that
inhibition of HLE by mucin involves binding of the positively charged HLE
molecules to the negatively charged sulfated carbohydrates in the mucin.
Mucin was also found to substantially reduce the antiprotease activity of
secretory leukocyte protease inhibitor, a low molecular weight cationic
protein known to bind to mucin.
