Heparin and heparan sulphate are inhibitors of human leucocyte elastase.

1. Heparin and heparan sulphate strongly inhibited human leucocyte elastase activity in an automated assay using the soluble substrate, n-succinyl-(L-alanine)3-p-nitroanilide (50% inhibition of 250 microliters of 10 micrograms of human leucocyte elastase/ml was obtained with 80 microliters of 2.8 micrograms of heparin/ml and 8 micrograms of heparan sulphate/ml). Less significant inhibition at the same concentrations was seen with the other glycosaminoglycans tested: hyaluronic acid and chondroitin sulphates A-C. 2. Heparin and heparan sulphate also strongly inhibited human leucocyte elastase activity towards insoluble human lung elastin, as determined by an e.l.i.s.a. for soluble elastin-derived peptides released by elastolytic activity on the elastin. This inhibition was shown not to be due to a direct interference of the glycosaminoglycans in the e.l.i.s.a. nor to the inhibition causing a change in the size of the elastin-derived peptides. However, unlike the chromogenic assay with n-succinyl-(L-alanine)3-p-nitroanilide as substrate, where heparin was the more effective inhibitor, in this assay system heparan sulphate was the more effective inhibitor (50% inhibition of 100 microliters of 50 ng of human leucocyte elastase/ml was obtained with 100 microliters of 4.5 micrograms of heparin/ml and 0.8 microgram of heparan sulphate/ml). These results suggest that heparin and heparan sulphate, as components of cellular and basement membranes, are likely to have a role in protecting structural proteins, such as elastin, from the proteolytic activity of human leucocyte elastase.(ABSTRACT TRUNCATED AT 250 WORDS)