Oxidative autoaggression by phagocytes in human peritonitis

Abstract

In 60 abdominal exudates from patients with the diagnosis of either acute or persistent (chronic) peritonitis, indicators of phagocyte-derived oxidative systems (myeloperoxidase, chemiluminescence) and proteases (elastase) were measured. These exudates reveal a picture of maximal inflammatory activation. Both types of exudates (30 each) showed a significant influx of inflammatory cells, with the mean leucocyte count being 73,000 microL and 32,000 microL-1 respectively. Local myeloperoxidase concentrations were approximately 1000-fold greater than that of normal plasma. Spontaneous and elicitable chemiluminescence--indicators of phagocyte respiratory burst activity--were dramatically increased. In addition, levels of extracellularly released elastase (from neutrophils) were found to be up to about 1000-fold that of normal plasma values. Although most of the elastase detected in the exudates was complexed with alpha 1-proteinase inhibitor (alpha 1 PI), enzymatically active elastase could be measured in approximately 60% of the samples being investigated. As there was an excess of immunoreactive alpha 1 PI in these exudates, the free elastase activity implies that much of the alpha 1 PI was inactive, presumably subjected to oxidative destruction. Moreover, a trypsin-inhibitory activity to antigen ratio below 1 (mean = 0.81) in 75% of the purulent exudates indicated also partial proteolytic degradation of alpha 1 PI. In contrast, 16 clear exudates (no bacteria, white cell count below 500 microL-1) taken from the non-infected peritoneal cavity of patients undergoing intra-abdominal surgery revealed a similar permeability increase of the peritoneum but did not show relevant oxidative and proteolytic activity or destruction of alpha 1 PI compared with purulent specimens. Thus, only the inflammatory process of peritonitis appears to result in an overwhelming local phagocytic activity that initiates and maintains protease inhibitor consumption and/or inactivation. The tremendous oxidative potential found in purulent exudates may cause destruction in a wide variety of defence systems.

Inhibition of adhesion and proliferation of peritoneally disseminated tumor cells by pegylated catalase

“…The ROS produced are intended to destroy invading organisms and damaged tissues. Despite these beneficial effects, the overwhelming oxidative stress can result in additional tissue destruction [31]. It has also been reported that low levels of ROS are involved in various metastatic processes, such as adhesion, invasion and proliferation [12][13][14][15][16]32].…”

Proteinase activity regulation by glycosaminoglycans

“…The proteinase inhibitors responsible for the control of NE activity are α 1 -proteinase inhibitor (α 1 -PI), α 2 -macroglobulin, and mucus proteinase inhibitor. In vivo, the inhibition of NE by mucus proteinase inhibitor and α 1 -PI may be affected by compounds present at the site where the inhibition reaction takes place, with oxidants released by polymorphonuclear neutrophils present at sites of inflammation reducing the capacity of NE inhibition by α 1 -antitrypsin (33) and α 1 -PI (34). On the other hand, when heparin is administered to some patients, it will bind NE and decrease its rate of inhibition by α 1 -PI (5).…”

Less stress, more success? Oncological implications of surgery-induced oxidative stress

“…Reactive oxygen species (ROS) have traditionally been viewed as a destructive force 1 2. However, there is growing evidence to demonstrate that ROS have Jekyll and Hyde characteristics which contribute significantly to tumour cell development 3–6.…”

“…Traditionally, the acute phase response associated with surgical trauma has been proposed as the main contributor to elevation of ROS levels postoperatively 1 2. However, there is an untold side to this story in the form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) enzymes which are now known to be overexpressed in non-phagocytic cells such as cancer cells 20.…”