Receptor-Mediated Endocytosis of Thrombin-Antithrombin III Complex by the Human Monocytoid Cell Line U937

Cytokeratin 18 Is Expressed on the Hepatocyte Plasma Membrane Surface and Interacts with Thrombin-Antithrombin Complexes

“…Thus, Takeya et al (48) demonstrated that TAT bound to a receptor distinct from the SECR. Similar to the findings of this present study, the SECR-binding pentapeptide did not inhibit TAT, or ␣-AC-cathepsin G complex binding to cells (48,50). Indeed, alterations in the SECR-binding pentapeptide consensus sequence for HCII have been shown to have no effect on HCII-thrombin complex binding to HepG2 cells (51).…”

“…However, this is not dissimilar to other studies which indicate low affinity TAT binding to SECR (10,12), as well as purified LRP (15). Specific TAT binding to monocytoid cells had a K d Ϸ 80 nM (48), while TAT binding to HepG2 cells was found to have a K d Ϸ 247 nM (49). In the present studies, the use of the SECR-binding pentapeptide did not inhibit 125 I-TAT binding to rabbit liver plasma membranes while a 20-fold molar excess of cold TAT inhibited binding by Ϸ50%.…”

“…This slow binding is not in keeping with the known very rapid removal rate for TAT in vivo. Moreover, some investigators have found no evidence for TAT binding to purified LRP (48). Recently a PN-1 peptide was found to be a potent inhibitor of PN-1-thrombin internalization by LRP, but this peptide was found not to inhibit PN-1-thrombin binding to the cell surface; supporting the possibility that TAT could bind to a receptor protein other than LRP (52).…”

Prothrombotic and Inflammatory Effects of Intravenous Administration of Human Immunoglobulin G in Dogs

“…Decreased TAT and FDP clearance via competition of IgG for cellular uptake is an unlikely explanation for the increased serum concentrations given that IgG is removed via Fc receptors on leukocytes, while TAT and FDP each bind to their own distinct receptors, many of which are on hepatocytes rather than macrophages. 22,23 Hyperviscosity of the circulating plasma due to massive infusion of the plasma protein preparation (hIVIgG) is thought to be a major contributor to thromboembolism in human patients receiving IVIgG therapy. 14,15 Approximately a 1.8 g/dL increase in plasma protein concentration has been reported to occur with a 2 g/kg infusion of hIVIgG over 2-5 days, and in that study, hyperproteinemia was a significant predictor of plasma hyperviscosity.…”

“…The increased FDP and TAT concentrations in this study suggest that hIVIgG somehow stimulates coagulation and fibrinolysis in dogs. Decreased TAT and FDP clearance via competition of IgG for cellular uptake is an unlikely explanation for the increased serum concentrations given that IgG is removed via Fc receptors on leukocytes, while TAT and FDP each bind to their own distinct receptors, many of which are on hepatocytes rather than macrophages 22,23 …”