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.