ALPHA(1)-MICROGLOBULIN DESTROYS THE PROTEINASE INHIBITORY ACTIVITY OFALPHA(1)-INHIBITOR-3 BY COMPLEX-FORMATION

The immunoregulatory plasma protein alpha(1)-microglobulin (alpha(1)-m ) and the proteinase inhibitor alpha(1)-inhibitor-3 (alpha(1)I(3)) for m a complex in rat plasma. In the present work, it was demonstrated th at the alpha(1)I(3).alpha(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 indica ted that the thiolester bond of the alpha(1)I(3).alpha(1)-m complex wa s broken. The alpha(1)I(3).alpha(1)-m complex was cleared from the cir culation much faster than native alpha(1)I(3), with a half-life of app roximately 7 min. Structurally, however, the alpha(1)I(3).alpha(1)-m c omplex was similar to native alpha(1)I(3) rather than alpha(1)I(3) cle aved by proteinases. It is speculated that the role of alpha(1)-m is t o destroy the function of alpha(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 for mation of complexes between alpha(1)-m and alpha(1)I(3) may serve as a mean to regulate the function of alpha(1)-m since its complex with al pha(1)I(3) is taken up rapidly by cellular receptors for alpha-macrogl obulins.