In this work we evaluate the proteolytic state of plasma
alpha2-macroglobulin in
acute pancreatitis. In addition, the plasma activity of
matrix metalloproteinase-2 (MMP-2), MMP-9 and
serine proteinases were analyzed. A total of 33 patients with
acute pancreatitis were studied, of whom 16 were diagnosed as having mild and 17 as having severe
acute pancreatitis. In the latter group, three patients progressed to multi-organ failure and died as a consequence of these complications. The proteolytic fragmentation of
alpha2-macroglobulin was evaluated by Western blotting, whereas the plasma activity of MMP-2, MMP-9 and
serine proteinases was evaluated by
gelatin zymography. Enhanced fragmentation of
alpha2-macroglobulin was detected in severe
acute pancreatitis patients with
multiple organ failure and lethal complications. In this same patient group, increased plasma activity of the active forms of MMP-2 and MMP-9, as well as
serine proteinases, was apparent. In addition, we demonstrate that
chymotrypsin-like
proteinases could be the principal cause of
alpha2-macroglobulin degradation in this group of patients. Our results indicate that secondary proteolysis of
alpha2-macroglobulin promotes impaired control of extracellular proteolytic activity, leading to local and distant tissue
injuries during severe
acute pancreatitis. Finally, the structural evaluation of plasma
alpha2-macroglobulin could be used as a prognostic marker of the severity of
acute pancreatitis.