COMMERCIAL PLASMA ALPHA(1)-ANTITRYPSIN (PROLASTIN(R)) CONTAINS A CONFORMATIONALLY INACTIVE, LATENT COMPONENT

Fractionated plasma alpha(1)-antitrypsin is widely-used as replacement therapy in patients with Z alpha(1)-antitrypsin deficiency-related em physema, We have recently shown that purified antitrypsin may be induc ed to adopt an inactive latent conformation by heating at high tempera tures in stabilizing concentrations of sodium citrate, Such a conforma tion was predicted to be present in commercial preparations of antitry psin, as these require heating under similar conditions for viral inac tivation. Native antitrypsin was purified from plasma, and commercial antitrypsin (Prolastin(R)) was obtained from Bayer Corporation, Wester n blot analysis of transverse urea gradient (TUG) gels showed that com mercial antitrypsin migrated as two bands: one with an unfolding profi le of native antitrypsin and the second with a profile of latent antit rypsin, A latent fraction, comprising approximately 8% of the total an titrypsin, was separated from the native antitrypsin in Prolastin(R) b y anion exchange chromatography. The specific activity of this latent form against bovine alpha-chymotrypsin increased from 1 to 2% to 50% o ver 3 h after refolding from 6 M guanidine hydrochloride. These data s how that commercial antitrypsin contains a latent component, The signi ficance of this conformation in vivo is unknown, although Prolastin(R) has shown few adverse side-effects in prolonged clinical usage.