A unique pathway for the plasma elimination of alpha 2-antiplasmin-protease complexes in mice.
Radiolabeled alpha 2-antiplasmin cleared slowly from the circulation of mice. Complex formation with either plasmin or trypsin resulted in a significant increase in the plasma elimination rate of the protease inhibitor. Approximately 20 min and 14 min were required for 50% of the injected alpha 2-antiplasmin-plasmin and alpha 2-antiplasmin-trypsin to clear from the circulation, respectively. Significant competition was observed when radiolabeled alpha 2-antiplasmin-plasmin was cleared in the presence of a large molar excess of unlabeled alpha 2-antiplasmin-plasmin. alpha 1-Antitrypsin-trypsin failed to complete with radiolabeled alpha 2-antiplasmin-plasmin even when present at 2000 fold molar excess. Organ distribution studies localized the major site of alpha 2-antiplasmin-plasmin clearance in the liver. Microscopic autoradiography data suggested that the cell responsible for the clearance pathway was the hepatocyte.
D000818:Animals; D001667:Binding, Competitive; D005260:Female; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D010447:Peptide Hydrolases / Q000378:metabolism*; D010949:Plasma / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D011869:Radioligand Assay; D000979:alpha-2-Antiplasmin / Q000378:metabolism*
D011480:Protease Inhibitors; D000979:alpha-2-Antiplasmin; D010447:Peptide Hydrolases