α1-Microglobulin Destroys the Proteinase Inhibitory Activity of α1-Inhibitor-3 by Complex Formation (∗)

The immunoregulatory plasma protein α1-microglobulin (α1-m) and the proteinase inhibitor α1-inhibitor-3 (α1I3) form a complex in rat plasma. In the present work, it was demonstrated that the α1I3•α1-m complex has no inhibitory activity, the bait region was not cleaved by low amounts of proteinases, and it was unable to covalently incorporate proteinases. The results also indicated that the thiolester bond of the α1I3•α1-m complex was broken. The α1I3•α1-m complex was cleared from the circulation much faster than native α1I3, with a half-life of approximately 7 min. Structurally, however, the α1I3•α1-m complex was similar to native α1I3 rather than α1I3 cleaved by proteinases. It is speculated that the role of α1-m is to destroy the function of α1I3 by blocking the bait region and breaking the thiolester and causing its physical elimination by rapid clearing from the blood circulation. It is also possible that the formation of complexes between α1-m and α1I3 may serve as a mean to regulate the function of α1-m since its complex with α1I3 is taken up rapidly by cellular receptors for α-macroglobulins.