Some properties of proteolysis by polymorphonuclear leukocyte granule extracts

Abstract

The extracts of granules of human polymorphonuclear leukocytes hydrolyzed a variety of proteins including human and bovine hemoglobin, human fibrinogen, human and bovine serum albumin, bovine elastin, and casein. The hydrolysis of all the proteins except fibrinogen and elastin was increased by addition of urea. Various inhibitors of trypsin, kallikrein, plasmin, C1r, C1s, and other proteolytic enzymes had no inhibitory effect. Slight inhibition was observed with polyanethol sulfonate and strong inhibition with normal human serum. Serum of patients with hereditary angioneurotic edema having no functional C1 esterase inhibitor was as effective in inhibiting the proteolysis as normal serum. The inhibitor was localized in 4S fractions of normal serum fractionated on Sephadex G200. Fractionation of normal serum by ammonium sulfate precipitation, Sephadex G200 filtration, and CM Sephadex chromatography did not result in appearance of inhibitory activity in more than one protein peak, suggesting the possibility that only one inhibitor might be responsible. Since all fractions which contained the inhibitor of proteolysis also contained α1 antitrypsin, since sera of patients having low α1 antitrypsin levels contained less inhibitory activity, and since antibodies against α1 antitrypsin reversed the inhibition obtained from normal serum, the inhibition of proteolysis may be attributed to α1 antitrypsin.