HEPATIC AND EXTRAHEPATIC CLEARANCE OF CIRCULATING HUMAN LACTOFERRIN -AN EXPERIMENTAL-STUDY IN RAT

Lactoferrin, unlabelled or I-125-labelled by 2 different methods, was given intravenously to rats. Blood, tissue and liver cell radioactivit y was measured. Both of the radiolabelled preparations were eliminated by the liver, and some deposited extrahepatically. One preparation fo rmed large aggregates - here 90% of the hepatic uptake occurred in the Kupffer cells. The other preparation, consisting mostly of protein mo nomers but also dimers/oligomers/microaggregates, was taken up by hepa tocytes (63% of total liver uptake), liver endothelial cells (22%) and Kupffer cells (15%). On a per cell volume basis, lactoferrin uptake w as much more efficient by nonparenchymal cells compared to hepatocytes , which explains why immunomorphological staining only revealed lactof errin in the nonparenchymal liver cells. The study demonstrates that r adio-iodination of lactoferrin can affect its properties and handling, which may be important regarding contradictory reports on hepatic lac toferrin uptake. We conclude that both hepatocytes and nonparenchymal liver cells are involved in the blood clearance of lactoferrin, probab ly to a great extent owing to nonspecific mechanisms. Extrahepatic dep osition and exposure (for instance on vessel walls/glomeruli) suggests that lactoferrin can be available to circulating anti-lactoferrin aut oantibodies in autoimmune disease.