AJP - Gastrointestinal and Liver Physiology, Vol 257, Issue 4 524-G531, Copyright © 1989 by American Physiological Society

ARTICLES

Effects of endotoxin on iron uptake by the hepatocyte

B. J. Potter, B. Blades, T. A. McHugh, R. M. Nunes, O. Beloqui, P. A. Slott and J. H. Rand
Polly Annenberg Levee Hematology Center, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029.

Administration of endotoxins is often followed within 12-24 h by marked hypoferremia. Because the hepatocyte is the major site of both iron storage and transferrin synthesis, we have investigated the effects of an Escherichia coli endotoxin (lipopolysaccharide, LPS) on these parameters on isolated hepatocytes from normal Wistar rats (ND), rats previously treated intraperitoneally with 2.5 mg/kg (LD) or 25 mg/kg (HD) LPS, and control rats injected intraperitoneally with sterile saline (CD). No effects were observed on iron uptake from transferrin by ND cells incubated in vitro with up to 350 micrograms LPS/10(7) hepatocytes. There was also no significant difference in iron uptake between CD, HD, and LD hepatocytes 1 h after LPS injection. However, hepatocytes isolated 24 h after LPS administration took up iron significantly faster than controls. The uptake of non-transferrin-bound iron was also increased in HD and LD hepatocytes at 24 h but only in HD cells at 1 h. Transferrin binding was not altered in LPS-treated cells from ND rats but was depressed in cells from LPS-treated rats both at 1 h and at 24 h after injection. Transferrin receptor recycling was significantly increased at 24 h in cells from both LD and HD rats. Transferrin and total protein synthesis were also depressed at 1 h in LPS-treated rats, returning to normal values at 24 h. Direct preincubation of ND cells, however, failed to increase synthesis except at the highest concentrations of LPS. We conclude that LPS has an immediate (although indirect) effect on protein synthesis by the hepatocyte but not on iron uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				K.-y. Yeh, M. Yeh, and J. Glass Hepcidin regulation of ferroportin 1 expression in the liver and intestine of the rat Am J Physiol Gastrointest Liver Physiol, March 1, 2004; 286(3): G385 - G394. [Abstract] [Full Text] [PDF]

				S. Liu, D. J. Gallo, A. M. Green, D. L. Williams, X. Gong, R. A. Shapiro, A. A. Gambotto, E. L. Humphris, Y. Vodovotz, and T. R. Billiar Role of Toll-Like Receptors in Changes in Gene Expression and NF-{kappa}B Activation in Mouse Hepatocytes Stimulated with Lipopolysaccharide Infect. Immun., July 1, 2002; 70(7): 3433 - 3442. [Abstract] [Full Text] [PDF]

				C. Pigeon, G. Ilyin, B. Courselaud, P. Leroyer, B. Turlin, P. Brissot, and O. Loreal A New Mouse Liver-specific Gene, Encoding a Protein Homologous to Human Antimicrobial Peptide Hepcidin, Is Overexpressed during Iron Overload J. Biol. Chem., March 9, 2001; 276(11): 7811 - 7819. [Abstract] [Full Text] [PDF]