Human serum inhibitors of collagenase as revealed by preparative isoelectric focusing.

Single step separation of pooled normal human serum by means of preparative isoelectric focusing in the range from pH 3.5--9.8 revealed more heterogeneous inhibition of collagenolytic activity than previously reported. Essentially three inhibition zones were resolved. According to their electrophoretic behaviour the respective serum fractions displaying inhibitory activity were designated alpha-, beta- and gamma-collagenase inhibitors. The main component responsible for collagenase inhibition in the alpha-zone was found to be alpha 2-macroglobulin. In the beta-zone inhibitory activity focused around pH 6.3. In the gamma-range a non-dialysable cationic component focusing at pH 9.2 was also able to decrease collagenolytic activity derived from rheumatoid arthritis synovial culture supernatant. These findings were supported by single step separation of serum on DEAE-anion exchange chromatography.