抄録
This paper focuses on the process of the formation of complexes between α2-macroglobulin (α2-M) and fibrinolytic enzymes, which play an important role in the intravascular fibrinolytic activity, and on the clearance of these complexes from the circulating blood through regulatory mechanisms, especially with reference to the mechanism involving the LDL receptor-related protein/α2-Macroglobulin receptor (LRP/α2-MR).
α2-M had previously been considered as one of the plasmin inhibitors, but is now also considered as a binding protein of certain proteases and of non-proteolytic amines, peptides, and proteins.
The proteases-like tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA) showed decreased activities when they were bound to α2-M. But under these circumstances the activities of two-chain t-PA (tct-PA), which are more promptly suppressed by Plasminogen activator inhibitor-1 (PAI-1) than are those of native single-chain t-PA, are not only preserved but also protected from this specific inhibitor. We also demonstrated in in vivo studies that the activities of tct-PA in the circulating blood showed a reverse correlation with the values of the PAI-1/α2-M ratio, indicating that the intervention of α2-M in the reaction between t-PA and PAT-1 enhances fibrinolysis.
The clearance of exogenous t-PA from the circulating blood showed a biphasic mode (initial phase and the terminal phase). Although the uptake of the t-PA-α2-M complex is performed by LRP/α2-MR, the removal of free t-PA is complicated. However, the initial phase of t-PA clearance would be mainly the responsibility of t-PA receptors (mannose and galactose receptors), and the terminal phase of that would be performed mainly by LRP/α2-MR.
Therefore, the roles of α2-M and LRP/α2-MR in the entire system participating in the regulation of the plasminogen-plasmin system would be important.
