Catabolism of circulating collagen in the Atlantic salmon ( Salmo salar )

The catabolic fate of circulating collagen (Col) in the Atlantic salmon ( Salmo salar ) was studied. Serum t 1/2 and organ distribution of circulating Col in salmon were determined using Col conjugated with l25 I‐tyramine cellobiose ( 125 I‐TC), a low molecular weight adduct which is trapped intralysosomally at the site of uptake. Intravenously administered l25 I‐tyramine cellobioselabelled Col type I was prepared either from salmon skin (sCol) or rat skin (rCol). Biphasic clearance kinetics of l25 I‐TC‐sCol in salmon were apparent, with 78% being removed from the circulation in an initial rapid α‐phase (t 1/2 (α) = 2.4 min), and 22% being removed more slowly in a terminalβ‐phase (t]2(β) = 25.8 min). Serum half life of 125 I‐TC‐rCol was found to be 5.4 min (in this type of experiment the number of data points allow the determination of only a monophasic decay slope). Approximately 90% of recovered radioactivity was found in the kidney of the fish. In comparative experiments, 74% of administered 125 I‐TC‐sCol was cleared from the circulation of rats during an initial rapid α‐phase with t l/2 (α) = 0.8 min, and 26% was eliminated in the terminal β‐phase with t 1/2 (β) = 7.2 min l25 I‐sCol was endocytosed and degraded in pure cultures of ral liver endothelial cells, which are the main site of clearance of circulating Col in the rat. Moreover, Col from the two species competed for the same receptor on cultured rat liver endothelial cells, Intravenous administration of tetramethyl rhodamine isothiocyanate‐labelled sCol (TRITC‐sCol) in salmon, and subsequent examination of sections of kidney in the fluorescence microscope, revealed that the fluorochrome was accumulated exclusively in discrete vesicles of sinusoidal lining cells. Analyses of kidney tissue 24h after intravenous administration of a mixture of fluorescein isothiocyanate‐labelled latex beads and TRITC‐sCol revealed no codistribution of the two fluorochromes, suggesting that the injected Col was taken up in cells different from macrophages. Purified pronephros macrophages prepared after simultaneous injections of stained beads and Col contained only fluorescein‐labelled latex particles. Interestingly, the cells which had accumulated TRITC‐sCol appeared to be equally distributed in both pronephros and the part of the kidney containing tubuli. We conclude that Col which gains access to the circulation of the Atlantic salmon is cleared mainly by uptake into sinusoidal lining cells of the kidney. These cells are distinct from phagocytosing macrophages, and morphologically similar to the highly specialized scavenging endothelial cells of mammalian liver sinusoids.