Microglobulin Destroys the Proteinase Inhibitory Activity of -Inhibitor-3 by Complex Formation

The immunoregulatory plasma protein α 1 -microglobulin (α 1 -m) and the proteinase inhibitor α 1 -inhibitor-3 (α 1 I 3 ) form a complex in rat plasma. In the present work, it was demonstrated that the α 1 I 3 •α 1 -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 α 1 I 3 •α 1 -m complex was broken. The α 1 I 3 •α 1 -m complex was cleared from the circulation much faster than native α 1 I 3 , with a half-life of approximately 7 min. Structurally, however, the α 1 I 3 •α 1 -m complex was similar to native α 1 I 3 rather than α 1 I 3 cleaved by proteinases. It is speculated that the role of α 1 -m is to destroy the function of α 1 I 3 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 α 1 -m and α 1 I 3 may serve as a mean to regulate the function of α 1 -m since its complex with α 1 I 3 is taken up rapidly by cellular receptors for α-macroglobulins.