Effects of iron loading and bacillus Calmette-Guerin on a glycoprotein recognition system on rat hepatic sinusoidal cells.
Experiments were performed to determine the effects of agents that modify Kupffer cells on the mannose-N-acetylglucosamine-glycoprotein receptor on hepatic sinusoidal cells. Cells were prepared by collagenase liver perfusion, centrifugation on Percoll gradients, and centrifugal elutriation. The uptake of 125I-labeled agalacto-orosomucoid (125I-AGOR), an N-acetylglucosamine-terminated glycoprotein, was greatest (53% of total uptake) by elutriator fractions containing equal proportions of endothelial and Kupffer cells ("mixed cell" fraction). Uptake was specific and time and concentration dependent. The apparent Km (0.4 mumol/L) and the patterns of inhibition by monosaccharides were similar in all the elutriator fractions, suggesting that only one class of receptor was present. The highest apparent maximal velocity (18 pmol/hr/5 X 10(6) cells) was found in the mixed cell fraction, indicating this fraction contained the highest proportion of receptor-bearing cells. Latex (0.8 micron) and bacillus Calmette-Guerin pretreatments did not influence the hepatic uptake of the glycoprotein in vivo. Iron sorbitol significantly reduced hepatic glycoprotein uptake and caused a twofold increase in the proportion of the ligand remaining in the circulation. Uptake of 125I-agalacto-orosomucoid by cells from latex-treated rats was similar to controls, but uptake by bacillus Calmette-Guerin-treated rat cells was only 25% of control uptake. This was related to a marked increase in sinusoidal cell number caused by bacillus Calmette-Guerin. In contrast, iron sorbitol caused a selective suppression of 125I-agalacto-orosomucoid uptake (10% of control uptake) by cells in the mixed cell fraction. This study showed that maximal uptake of 125I-agalacto-orosomucoid was by elutriator fractions containing equal proportions of endothelial and Kupffer cells and that iron sorbitol suppressed ligand uptake by these cells, possibly by influencing the mannose-N-acetylglucosamine receptor on Kupffer cells.
D000818:Animals; D001500:BCG Vaccine / Q000494:pharmacology*; D006023:Glycoproteins / Q000378:metabolism*; D066298:In Vitro Techniques; D007501:Iron / Q000494:pharmacology*; D007728:Kupffer Cells / Q000187:drug effects; D007840:Latex / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D051381:Rats; D011919:Rats, Inbred Strains; D011971:Receptors, Immunologic / Q000032:analysis / Q000187:drug effects*
D001500:BCG Vaccine; D006023:Glycoproteins; D007840:Latex; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D011971:Receptors, Immunologic; C032193:glycoprotein receptor GPIb-IX; D007501:Iron