The role of protease in immunoregulation

Whilst immunodepression is widely recognized in patients subject to trauma or chronic disease, the mechanism of this process is poorly understood. We found that most of the lymphocyte suppressive activity of plasma from severely ill patients was attributable to the protein alpha 2-macroglobulin (alpha 2 M) and low molecular weight peptide (less than 10000). The only major variation in alpha 2 M concentration was found in patients subject to trauma, when it was depressed at times of high plasma suppressive activity. In order to explain qualitative immunosuppressive differences in alpha 2 M we studied its functional role as the main route for binding and degrading proteolytic enzyme (protease). In normal plasma minor degrees of protease complex formation to alpha 2 M caused greatly increased suppressive activity due principally to alpha 2 M and the abnormal appearance of low molecular weight peptide (less than 10000). Study of protease inhibitor function in patients suffering from acute or chronic illness suggested that in these patients their plasma becomes immunosuppressive due to inadequate handling of protease, resulting in alpha 2 M-protease complexes or inhibitory peptides persisting in the circulation. Opportunities for background immunoregulation by altering protease metabolism are considered.