[Inter-alpha-trypsin inhibitor and its plasma and urine derivatives]

Inter-alpha-trypsin inhibitor (ITI) is a serine protease inhibitor present in human plasma at a concentration of 0.4 to 0.5 g/l. Its molecular weight is about 220 kDa. This glycoprotein is a complex of at least three kinds of subunits: two heavy chains and a light one carrying the antiproteasic activity and corresponding to the urinary trypsin inhibitor (UTI). UTI is a proteoglycan containing a chondroitin sulfate side chain; the stability of the ITI complex is clearly dependent upon the integrity of the glycosaminoglycan part of UTI. ITI is mainly synthetized in liver; in case of inflammatory disorders ITI which is very sensitive to numerous proteases, namely elastase and cathepsin G released by stimulated neutrophils, is degraded into lower molecular weight derivatives present in plasma, among which UTI excreted in urine. The physiological role of ITI still remains elusive; ITI may be considered as a precursor of smaller inhibitors. Owing to their small size, they could secondarily diffuse into the extracellular space and reach tissues to protect them from proteolytic destruction. However, their ability to inhibit human granulocytic elastase seems to be too low for their physiological relevance. UTI was recently shown as exhibiting a growth stimulatory activity for human endothelial cells. In addition, UTI exhibits anti-inflammatory effects, the mechanism of which has not yet been elucidated. Owing to its pharmacological properties, UTI might be of therapeutic value in the treatment of inflammatory disorders. At last, the excretion of UTI, which seems to be depending upon neutrophil activation can be considered as a useful test for detecting and monitoring infections.