ROLE OF LIVER ENDOTHELIAL AND KUPFFER CELLS IN CLEARANCE OF HUMAN C1Q IN RATS

In the present study the contribution of rat liver endothelial cells (EC) and Kupffer cells (KC) in the clearance of human (hu) C1q in rats was investigated. In untreated rats and rats depleted from KC the clearance kinetics and the tissue distribution of hu Clq were measured. In untreated rats, the clearance of hu Clq occurred in a monophasic manner with a half-life of 66 +/- 26.7 min.The clearance of hu Clq in KC-depleted rats was delayed significantly (p < 0.001) and occurred with a half-life of 217 +/- 78.8 min. Fifteen min after injection, 11 +/- 3.5% of hu Clq was found in the liver of untreated rats and 8 +/- 1.4% was found in the liver of KC-depleted rats.The percentage non-trichloroacetic acid precipitable activity in the circulation, as a measure for degradation of Clq, reached a level of 11.6 +/-5.6% at 240 min in untreated rats compared with 4.6 +/- 5.8% in KC-depleted rats. Double immunofluorescence staining 5 min after administration of C1q in untreated rats, revealed that Clq was associated with KC and EC in the liver. Fifteen minutes after i.v. injection of hu C1q, there was an uptake of Clq in the hepatocytes. In KC-depleted rats, 5 min after administration of hu C1q, C1q was bound to the EC. Fifteen minutes after injection, Clq was also found in the hepatocytes. Electron microscopical studies revealed that Clq binds to EC, and that it is internalized in the hepatocytes and KC. The clearance of hu C1q in untreated rats was inhibited by preadministration of high concentrations of bovine C1q. These data show that rats depleted from KC are able to bind, internalize and degrade C1q, and that EC may play a role in the handling of Clq and C1q bound to immune complexes.