AJP - Gastrointestinal and Liver Physiology, Vol 248, Issue 4 463-G469, Copyright © 1985 by American Physiological Society
Interaction of human lactoferrin with the rat liver
M. T. Debanne, E. Regoeczi, G. D. Sweeney and F. Krestynski
Binding of human lactoferrin (hLf) by purified rat liver plasma membranes
was studied to clarify whether the liver possesses specific hLf receptors.
The binding was rapid between 4 degrees and 37 degrees C, with a pH optimum
close to 5.0. At 22 degrees C and in glycine-NaOH (5 mM, pH 7.4) containing
150 mM NaCl and 0.5% albumin, 1 microgram of membrane bound a maximum of
11.8 ng hLf. The dissociation constant of the interaction was 1.6 X 10(-7)
M. Other proteins of high isoelectric points (lactoperoxidase, lysozyme,
and particularly salmine sulfate) and a piperazine derivative inhibited hLf
binding in a concentration-dependent manner. In contrast, monosaccharides
(galactose, N-acetylgalactosamine, mannose, and fucose) were ineffective.
By omitting NaCl from the incubation buffer, binding was increased
3.6-fold. Erythrocyte ghosts bound hLf less firmly and alveolar macrophages
more firmly than hepatic plasma membranes. Liver cell fractionations
performed after the intravenous injection of labeled hLf showed that
approximately 88% of the hepatic radioligand was associated with
parenchymal cells. When binding was expressed per unit of cell volume,
however, more hLf was present in nonparenchymal than in parenchymal cells,
implying that the above value was determined by the relative cell masses
rather than affinities alone. It is concluded that the binding of hLf by
hepatic plasma membranes is electrostatic, i.e., is mediated by the
cationic nature of the ligand, and that it is explicable in terms of a
"specific nonreceptor interaction" of the generalized type proposed by
Cuatrecasas and Hollenberg (Adv. Protein Chem. 30: 251-451, 1976).
