Clearance and metabolism of circulating pancreatic proelastase in the rat

A rat model has been employed to study the mechanism of clearance of pancreatic proelastase from the circulation. The clearance of 125I-labeled proelastase was shown to be biphasic, with a half-life for clearance of free 25,000-dalton proelastase of approximately 7-10 min. A slow component of clearance possibly due to proelastase associated with plasma protease inhibitors was also observed. At 10 min after injection of 125I-labeled proelastase into the circulation, the major fraction of the 125I was found to be localized in the kidney. However, appearance of 125I in urine is slow, with 16 h being required for excretion of 50% of the injected 125I as acid-soluble material. Subcellular localization experiments on homogenates of kidneys removed at 10 min postinjection revealed that the majority of the 125I-labeled material was associated with the mitochondrial and lysosomal fraction. Sucrose-gradient centrifugation studies of this fraction demonstrated that the labeled material passes from the membrane fraction to the lysosomal fraction with time. These data demonstrate that the rat kidney constitutes the major site for both circulatory clearance and catabolism of circulating pancreatic proelastase.