Uptake and degradation in vivo and in vitro of laminin and nidogen by rat liver cells.
Laminin antigens are known to be present in the blood of normal individuals. In the present study we have investigated the fate of laminin-related molecules in the circulation. After intravenous injection in rats, the native laminin-nidogen complex, as well as the separated proteins, were rapidly eliminated from the blood (half-lives 2-10 min) by the liver. The large laminin fragments E1 and E8 (Mr 400,000 and 280,000 respectively), which contain the major cell-adhesion-promoting activities of laminin, were also cleared from the blood mainly by the liver, but the rate of uptake was an order of magnitude lower for these fragments than for laminin. This indicates that the uptake of laminin did not occur via cell-adhesion receptors. The endothelial cells of liver were the most important cell type in the uptake of laminin-nidogen complex, nidogen, laminin and fragment E1, whereas the parenchymal cells were responsible for more than 50% of the uptake of E8 in the liver. Studies in vitro with cultured liver endothelial cells and parenchymal cells demonstrated that the ligands were endocytosed and degraded independently of plasma factors. The results reveal that the level of laminin antigens in blood is a very complex parameter. It is not only dependent on the turnover of basement membranes, but also on the degree of degradation of the material released into the blood and on the functional state of the liver, particularly the liver endothelial cells.
Smedsrød
B
B
Instiute of Medical Biology, University of Tromsø, Norway.
Paulsson
M
M
Johansson
S
S
D000818:Animals; D001485:Basement Membrane; D002478:Cells, Cultured; D007797:Laminin / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D009363:Neoplasm Proteins / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains
D007797:Laminin; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C029967:nidogen