The hepatic uptake of 59Fe from diferric rat and rabbit asialotransferrins and from human transferrin lacking two sialyl residues was investigated in rats in experiments lasting for 1 hr. The 59Fe attached to either of these preparations disappeared from the plasma more rapidly than the 59Fe introduced with the unmodified respective parent proteins. Most of the 59Fe activity that had disappeared from the circulation could be recovered with the liver. Studies with double-labeled (125I, 59Fe) preparations showed that the enhanced 59Fe clearance was not associated with increased catabolism of the modified transferrins. Prolonged, heavy alcohol consumption, as shown by others, results in the appearance of sialic acid-deficient transferrin (two residues missing) in human serum. We suggest that the increased capacity of transferrin deficient in sialic acid to selectively deposit iron in the hepatocyte may be of significance for the development of the hepatic siderosis observed in alcoholism.

Alcoholism↗

PubMedDate not supplied

Observations with a residualizing label in use to map the catabolic sites of plasma proteins.

Rat albumin, immunoglobulin G, transferrin, and aglycotransferrin were prepared for the comparison of their sites of degradation in rats. Iodotyramine-cellobiose was used as the residualizing label and a tyrosine-iodinated portion of the corresponding protein was used as the marker of extracellular undegraded protein. Each protein yielded a distinct distribution (or map) of catabolic activity throughout the body when expressed as percent dose accumulated per gram of tissue. The maps for albumin and transferrin were broadly comparable, whereas those for immunoglobulin G and aglycotransferrin were markedly different. As a whole entity, the liver appeared to top the list of organs/tissues contributing to the degradation of albumin and transferrin. Additional experiments aimed at facilitating the interpretation of results with residualizing labels were carried out with denatured albumin, asialofetuin, and human asialotransferrin type 3. These showed that various types of cells retained the label for markedly different periods of time. We feel, therefore, that the technique is more suited for making comparative measurements than for obtaining degradation rates as absolute values in a given anatomical location.

Animals↗

PubMedDate not supplied

Interaction of transferrin with rat alveolar macrophages.

Binding of rat transferrin to isolated alveolar macrophages was investigated in the 0.125 nM to 2 microM range. Computer analysis of the data revealed two classes of binding sites, a small number (< 1000 exposed/cell) having high affinity (dissociation constant (Kd), 3.4 nM) and a large number (approximately 4 x 10(6)/cell) having low affinity (Kd 48 microM). Measurements with a monoclonal antibody to the rat transferrin (rTf) receptor yielded values in the same range as the high-affinity sites derived from studies of ligand binding. Binding to the low-affinity sites at pH 5.8 was nearly one order of magnitude stronger than that at pH 7.3. Bovine lactoferrin (12 microM), cationized bovine serum albumin (14 microM), L-arginine (50 mM), and L-lysine (50 mM) did not compete against rTf binding to the low-affinity sites. Removal of an average of 2.6 x 10(8) sialyl residues from each cell did not affect binding. Heparan sulphate proteoglycan purified from alveolar macrophages bound strongly to immobilized rTf, thus raising the possibility that the low-affinity interaction of transferrin with these cells may be mediated, at least in part, by this glycosaminoglycan.

Animals↗

PubMedDate not supplied