Alpha 1-proteinase inhibitor is the serum regulator of the activity of p57, a C3-cleaving proteinase present in human erythrocyte membranes.

Human erythrocytes express at the membrane level a p57 serine proteinase which cleaves C3, the third component of complement. We demonstrated herein that human serum carries an inhibitory activity against this p57 membrane proteinase. Purification allowed to identify this inhibitor as the alpha 1-proteinase inhibitor (alpha 1-PI) on the basis of its molecular weight, antigenicity and amino acid sequence identity. Data demonstrated that alpha 1-PI is the unique and strong serum inhibitor of the p57 proteinase activity: inhibition studies showed that alpha 1-PI inhibited p57 proteinase activity with a kass value of 10(5) M-1 s-1. Inhibition of p57 proteinase by alpha 1-PI was due to formation of a SDS-stable complex between both components. We suggest that inhibition of the membrane p57 proteinase activity by serum alpha 1-PI may be involved in the regulation of C3 fragment generation and/or in clearance in liver of C3b bearing immune complexes by erythrocyte-CR1.