␣ 1 -Acid glycoprotein, one of the major acute phase proteins, was found to interact with plasminogen activator inhibitor type 1 (PAI-1) and to stabilize its inhibitory activity toward plasminogen activators. This conclusion is based on the following observations: (a) ␣ 1 -acid glycoprotein was identified to bind PAI-1 by a yeast two-hybrid system. Three of 10 positive clones identified by this method to interact with PAI-1 contained almost the entire sequence of ␣ 1 -acid glycoprotein; (b) this protein formed complexes with PAI-1 that could be immunoprecipitated from both the incubation mixtures and blood plasma by specific antibodies to either PAI-1 or ␣ 1 -acid glycoprotein. Such complexes could be also detected by a solid phase binding assay; and (c) the real-time bimolecular interactions monitored by surface plasmon resonance indicated that the complex of ␣ 1 -acid glycoprotein with PAI-1 is less stable than that formed by vitronectin with PAI-1, but in both cases, the apparent K D values were in the range of strong interactions (4.51 ؉ 1.33 and 0.58 ؉ 0.07 nM, respectively). The on rate for binding of PAI-1 to ␣ 1 -glycoprotein or vitronectin differed by 2-fold, indicating much faster complex formation by vitronectin than by ␣ 1 -acid glycoprotein. On the other hand, dissociation of PAI-1 bound to vitronectin was much slower than that from the ␣ 1 -acid glycoprotein, as indicated by 4-fold lower k off values. Furthermore, the PAI-1 activity toward urokinase-type plasminogen activator and tissue-type plasminogen activator was significantly prolonged in the presence of ␣ 1 -acid glycoprotein. These observations suggest that the complex of PAI-1 with ␣ 1 -acid glycoprotein can play a role as an alternative reservoir of the physiologically active form of the inhibitor, particularly during inflammation or other acute phase reactions.
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