AJP - Gastrointestinal and Liver Physiology, Vol 264, Issue 1 112-G117, Copyright © 1993 by American Physiological Society
Lactoferrin interferes with uptake of iron from transferrin and asialotransferrin by the rat liver
W. L. Hu, E. Regoeczi, P. A. Chindemi and M. Bolyos
Department of Pathology, McMaster University Health Sciences Centre, Hamilton, Ontario, Canada.
Intravenous injection of bovine or human lactoferrin (6.25 x 10(-2)
mumol/100 g body wt) in rats resulted in marked reduction of hepatic iron
uptake from transferrin and asialotransferrin. The effect was dose
dependent, saturable at approximately 5 mg/100 g body wt, and independent
of lactoferrin's iron content. At this dose level, iron uptake from
transferrin was reduced by 28% and from asialotransferrin by 43% in
experiments lasting 90 min. Bovine lactoperoxidase, another basic protein,
was similarly effective. The clearance of asialofetuin and pinocytosis of
polyvinylpyrrolidone remained unaffected. Perfusion of isolated rat livers
at 4 degrees C showed a strong reduction in asialotransferrin binding in
the presence of lactoferrin. Chromatography of hepatic heparan sulfate
proteoglycan on immobilized lactoferrin, lactoperoxidase,
asialotransferrin, and transferrin showed that it possessed affinity for
each of these proteins, more for the first two than the latter two. Heparan
sulfate proteoglycan binding and efficacy in reducing hepatic iron uptake
were also studied after selective modifications of positively charged amino
acids in these proteins. The data obtained are compatible with the
hypothesis that lactoferrin and other proteins with similarly high affinity
for hepatic heparan sulfate exert their negative effect on iron uptake by
preventing transferrin binding to the proteoglycan. The possibility is thus
raised that the large number of low-affinity transferrin binding sites
reported by earlier investigators for the liver may be heparan sulfate
molecules.
