Thyrotropin (10 gM) inhibited the antiviral activity of interferon. When added after interferon, thyrotropin (TSH) had no effect on antiviral activity. There was also no inhibition of interferon action in cells washed with medium between incubations with TSH and interferon.125I-Labeled TSH and 125I-labeled cholera toxin could bind to preparations of mouse L-cell plasma membranes. The binding was specific in that it was prevented by unlabeled thyrotropin or cholera toxin, but not by insulin, glucagon, prolactin, growth hormone, human chorionic gonadotropin, or luteinizing hormone.Mouse interferon inhibited 125I-labeled TSH binding to L-cell plasma membranes. The effect of mouse interferon on 125I-labeled cholera toxin binding was more complex, inhibition occurring only after an initial enhancement at low interferon concentrations. A 10-fold higher concentration of interferon was required to inhibit 25I-labeled cholera toxin binding as compared to 25I-labeled TSH binding. Mouse interferon was also able to displace bound 125I-labeled TSH, but not bound 125I-labeled cholera toxin. The interferon interaction with cell membranes was temperature-sensitive.Human interferon could induce changes in binding of 125I-labeled TSH and 125I-labeled cholera toxin to mouse L-cell plasma membranes similar to those induced by mouse interferon. Mouse interferon induced similar changes in plasma membranes of human KB-3 cells, which are insensitive to both human and mouse interferons. In view of these results, the species specificity of interferons does not appear to reside solely at the point of the initial interaction with their binding sites. The mechanism by which thyrotropin (TSH) and cholera toxin transmit their message to the cell is believed to require a multistep sequence of events whose main contributors are, in turn, a specific ganglioside or ganglioside-like receptor structure, a significant alteration in the state of the membrane, an effector-responsive adenylate cyclase, and cell metabolism susceptible to regulation by the increased production of adenosine 3':5'-cyclic monophosphate (1)(2)(3)(4).Interferon initiates an antiviral state by interacting with receptors which, like those for cholera toxin or TSH, may be gangliosides or ganglioside-like structures containing an oligosaccharide moiety as a critical feature of their structure (5-7). The evidence for a ganglioside or a ganglioside-like structure of the interferon binding site is: Phaseolus vulgaris phytohemagglutinin blocks interferon action (5); Sepharose-bound interferon loses its antiviral activity after preincubation with gangliosides (6); soluble interferon binds to Sepharose-bound gangliosides (6); interferon binding to gangliosides is inhibited by phytohemagglutinin (6); and sialyl-lactose reverses the ability of gangliosides to inhibit the action of interferon (7).The B protein of cholera toxin and the # subunit of TSH appear to carry the primary determinants for their interaction with the ganglioside or ganglioside-like structures on the cell memb...

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Uptake of transferrin and iron by the rat liver was investigated by perfusion in vitro with 125I-59Fe-labeled rat transferrin and subcellular fractionation on sucrose density gradients. Most of the 125I-transferrin was located in a low-density vesicle fraction. The 59Fe was in three peaks, of lower, the same, and higher densities than the transferrin peak. Iron deficiency resulted in a large increase in transferrin and iron uptake into all subcellular fractions. When livers were perfused with increasing concentrations of transferrin the uptake into the different peaks of transferrin and iron increased in a curvilinear fashion, which indicated that uptake occurred by saturable and nonsaturable processes, both of which increased in iron deficiency. In contrast, the uptake of 131I-labeled rat serum albumin increased linearly with concentration, and there was no difference between control and iron-deficient livers. It is concluded that iron deficiency leads to an increase in the number of high-affinity transferrin receptors and receptor-mediated endocytosis of transferrin. It also increases a nonsaturable transferrin uptake process that is probably due to adsorptive, but selective, endocytosis of transferrin.

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