Inflammatory cells degrade inter-alpha inhibitor to liberate urinary proteinase inhibitors.

The relationship between inter-alpha inhibitor (I alpha I) and urinary proteinase inhibitor (UPI) was examined by comparing purified UPI with a proteolytic fragment of I alpha I (I'), and by demonstrating that inflammatory cells produce similar fragments under physiologic conditions. Purified I', derived by chymotrypsin digestion of I alpha I, was similar to UPI in apparent molecular weight (68,000-69,000), amino acid composition, immunoreactivity, and inhibitory activity against trypsin, chymotrypsin, and neutrophil elastase. The production of similar inhibitory fragments by murine peritoneal macrophages, human neutrophils, and a murine mast cell line was quantified. Neutrophils were most efficient at proteolyzing I alpha I. Comparison of the pattern of I alpha I degradation by neutrophil preparations with that by pure enzymes, suggested that both elastase and cathepsin G mediate neutrophil proteolysis of I alpha I. These proteinases may thus be responsible for inflammation-related increases in UPI-like inhibitor levels in vivo.