FATE OF CIRCULATING AMINO-TERMINAL PROPEPTIDE OF TYPE-III PROCOLLAGENIN CONSCIOUS PIGS

The amino-terminal propeptide of type III procollagen (PIIINP, M(r) 42 ,000) is a promising marker for the formation of type III collagen of granulation tissue in experimental and clinical studies. The disposal kinetics of circulating PIIINP is, however, almost unknown. In conscio us pigs with a thoracic duct-venous shunt, I-125-labeled PIIINP was in jected intravenously. The initial distribution volume was 2.2 liters, which was 1.7 times the plasma volume (P < 0.01). The disappearance cu rve was three-phased, with an initial steep decline (t1/2 58 min), fol lowed by two slower phases (t1/2 239 min and 289 h). Consecutive gel f iltrations showed that the initial slope of the plasma disappearance c urve corresponded to the plasma clearance of the intact PIIINP. The in itial plasma clearance was 26.5 ml plasma/min, whereas the urinary cle arance was 8.7 ml plasma/min (P < 0.01). The other components of the p lasma disappearance curve originated from the formation and disappeara nce of a high and a low molecular weight (MW) fraction as part of the degradation of PIIINP. The high MW fraction (approximately M, 90,000) was similar to a previously described, but not further characterized, PIIINP immunoreactive component. The existence of the low MW fraction (approximately M(r) 20,000) has not been reported before. The lymphati c recirculation of intact PIIINP was rapid, and the lymph-serum ratio was almost constant within 1 h of injection. We conclude that the t1/2 of circulating PIIINP is 58 min, that PIIINP escapes the circulation very quickly, and that the degradation of PIIINP includes at least two intermediary steps.