The Clearance of Heterologous Protein from the Circulation of Normal and Immunized Man12

Abstract

The plasma clear -ance rates of streptokinase, a protein antigenic to man, were studied in both normal and immune man. Preparations of streptokinase, bio-physically homogeneous, were trace labeled with ll31 and were used to determine plasma streptokinase levels. Intravenously injected streptokinase was cleared from the circulation at 2 distinct rates, the "fast" (average 50% plasma clearance time 18 minutes), and the "slow" (average 50% clearance time 83 minutes). The fast rate was a consequence of the combination of the antigen with its antibody, and the clearance of the complex. The "slow" rate was operative in the absence of plasma antibody and may be due to activity of the reticulo-endothelial system. Specific immunization of the patient resulted in an increase in the proportion of antigen cleared at the fast rate. Doses of up to 10 ug antigen N/kg body weight were used in immune man, and the lack of deleterious clinical response was thought to be due to the patient''s acquired ability to remove, sequestrate and destroy the antigen.