Plasma lysosomal enzymes in experimental and clinical endotoxemia

Endotoxins, which are lipopolysaccharide complexes derived from the cell walls of gram-negative bacteria, have been implicated in the pathogenesis of gram-negative septic shock. One possible mechanism of endotoxin-induced damage may involve an action at cell surface membranes resulting in cell injury and lysosomal enzyme release. In our experiments, the administration of purified E. coli endotoxin (2 mg/kg intravenously) to guinea pigs produced elevations in the plasma activity of the lysosomal hydrolases glucosaminidase, acid phosphatase and Cathepsin D of approx. 2-, 3- and 4-fold, respectively, at 5 h following endotoxin injection. Animals haemorrhaged to produce sustained hypotension that was greater than the reduction in blood pressure seen with endotoxin treatment, exhibited an elevation only in plasma Cathepsin D activity that was, however, significantly lower than the increase associated with endotoxemia. The three lysosomal hydrolases were also measured in man, including a control group, patients with gram-negative septic shock, other shock, gram-positive and gram-negative septicaemia without shock. Plasma Cathepsin D activity was significantly elevated (26-fold above control) in the group with gram-negative septic shock as compared to all other groups. Patients in the gram-negative septic shock group and the other shock group both had significantly greater glucosaminidase activity than controls. Our results suggest that plasma Cathepsin D measurements may be of diagnostic and prognostic value in the clinical management of gram-negative septic shock.