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 betwee n local fibrillogenesis and serum PIIINP is governed by the transport and possible degradation en route from tissue to circulation. Tn consc ious pigs, we investigated the transport of PIIINP from the knee cavit y into the circulation after intra-articular injection of radiolabelle d PIIINP followed by sequential sampling of thoracic duct lymph, serum and urine. Clearance from the joint space was evaluated by external d etection of I-131-HSA, used as co-tracer. Lymph samples were gel filtr ated to assess possible lymphatic degradation of the intact PIIINP. I- 125-PIIINP and I-131-HSA were found in thoracic duct lymph within 20 m in of the intra-articular injection. Both isotopes had a biphasic appe arance, with the first peak after 60 min and a larger peak after 150 m in. During the 6 h observational period 18% of the injected PIIINP was found in the lymph. Gel chromatography of lymph showed the fast forma tion of a small fraction with a lower MW than that of PIIINP, which su ggests that some degradation of PIIINP may occur through the lymphatic s. The half-life of the joint clearance of HSA by bulk flow was assess ed to be 8.3 h. The clearance of PIIINP from the joint was estimated t o be equal to that of HSA, which indicates that PIIINP leaves the join t space by bulk flow as has been proposed for HSA. Whereas the fractio nal amount of PIIINP in lymph and blood was lower than that of HSA, in urine the fractional amount of PIIINP was substantially higher than t hat of HSA. This may be the outcome of a more rapid irreversible degra dation of PIIINP than of HSA. We conclude that 1) PIIINP is cleared fr om 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 compartmen ts in a ratio different from that of HSA. Our observations suggest tha t serum PIIINP may be used as a marker of fibrillogenesis in normal or ganisms.