Progress of tissue injury in appendicitis involves the serine proteases uPA and PAI-1

Abstract

Objective. Serine proteases and the matrix metalloproteinases (MMPs) are key factors in the proteolytic cascade and participate in extracellular matrix (ECM) degradation. Fibrinolytic activators and inhibitors may have an effect on inflammatory cells, thereby modulating the inflammatory response. It is reasonable to assume that they may be implicated in the tissue injury in acute appendicitis that subsequently leads to appendix perforation. The purpose of this study was to investigate the expression and distribution of urokinase-type plasminogen activator (uPA) and plasminogen-activator inhibitor type 1 (PAI-1) in appendicitis. Material and methods. Expression of uPA and expression of PAI-1 were measured in tissue specimens from patients with appendicitis (n=30) and in control specimens (n=9), using the quantitative ELISA technique. Distribution of enzymes was studied with immunohistochemistry. The uPA and PAI-1 levels in the subgroups of appendicitis and controls were compared. Results. The overall expressions of uPA and PAI-1 were greater in appendicitis than in control specimens (p <0.001 and p<0.0001, respectively). Expressions of uPA and PAI-1 in phlegmonous (n=15), gangrenous (n=6) and perforated appendicitis (n=9) were all higher than those in controls (n=9), (p<0.01). Moreover, the PAI-1 level was elevated in perforated appendicitis compared with phlegmonous appendicitis (p<0.01). uPA staining was observed in connection with vascular endothelial cells and the serosa stained intensely in specimens from perforated appendicitis. Conclusions. The expression of uPA and especially the over-expression of PAI-1 seem to correlate to the progression of local inflammatory response in acute appendicitis.