LYMPHATIC CLEARANCE OF SYNOVIAL-FLUID IN CONSCIOUS PIGS - THE AMINOTERMINAL PROPEPTIDE OF TYPE-III PROCOLLAGEN

The aminoterminal propeptide of type III procollagen (PIIINP) in serum is employed as a direct marker of fibrillogenesis. The balance between local fibrillogenesis and serum PIIINP is governed by the transport and possible degradation en route from tissue to circulation. Tn conscious pigs, we investigated the transport of PIIINP from the knee cavity into the circulation after intra-articular injection of radiolabelled PIIINP followed by sequential sampling of thoracic duct lymph, serum and urine. Clearance from the joint space was evaluated by external detection of I-131-HSA, used as co-tracer. Lymph samples were gel filtrated to assess possible lymphatic degradation of the intact PIIINP. I-125-PIIINP and I-131-HSA were found in thoracic duct lymph within 20 min of the intra-articular injection. Both isotopes had a biphasic appearance, with the first peak after 60 min and a larger peak after 150 min. During the 6 h observational period 18% of the injected PIIINP was found in the lymph. Gel chromatography of lymph showed the fast formation of a small fraction with a lower MW than that of PIIINP, which suggests that some degradation of PIIINP may occur through the lymphatics. The half-life of the joint clearance of HSA by bulk flow was assessed to be 8.3 h. The clearance of PIIINP from the joint was estimated to be equal to that of HSA, which indicates that PIIINP leaves the joint space by bulk flow as has been proposed for HSA. Whereas the fractional amount of PIIINP in lymph and blood was lower than that of HSA, in urine the fractional amount of PIIINP was substantially higher than that of HSA. This may be the outcome of a more rapid irreversible degradation of PIIINP than of HSA. We conclude that 1) PIIINP is cleared from the joint space by bulk flow; 2) degradation of PIIINP en route to the circulation cannot be excluded, but is less than 10%, and 3) after disappearing from the joint, PIIINP is distributed in body compartments in a ratio different from that of HSA. Our observations suggest that serum PIIINP may be used as a marker of fibrillogenesis in normal organisms.