Serum protease inhibitors in the blood clearance of subtilisin A.

The plasma clearance of a broad spectrum bacterial protease, subtilisin A, as a function of its binding to serum protease inhibitors and antibodies has been studied in rabbits. When administered in trace quantities, 80% of the active radiolabelled enzyme formed complexes with α-macroglobulins and the remainder with α-antitrypsin. The formation of complexes with these inhibitors produced a 15-16 fold increase in the rate of elimination of the enzyme from the blood. Enzyme-α-macroglobulin complexes had the fastest elimination rates (half-life approximately 2 minutes), exceeding the speed by which the enzyme was eliminated as antigen-antibody complexes. The clearance of enzyme-α-antitrypsin complexes was considerably slower. A dual isotope technique was applied to the post mortem analysis of the quantitative distribution in the principal reticuloendothelial organs and in muscles of intravenously administered enzyme-inhibitor complexes. There were marked differences in this respect between complexes of enzyme formed with α-macroglobulins and with α-antitrypsin.