The role of lysophosphatides in cell injury

Septic shock, particularly that resulting from Escherichia coli endotoxemia, has been associated with vascular perfusion abnormalities but also has been associated with organ damage, in particular hepatic, renal, cardiac, and pulmonary dysfunction. These changes and the biochemical finding of uncoupled oxidative phosphorylation in isolated mitochondria have been reported to occur prior to the onset of vascular perfusion abnormalities. This conceivably could be accounted for on the basis of release of phospholipase A and increased fatty acids in that fatty acids are potent uncouplers of oxidative phosphorylation. These experiments were done in vivo on rat liver and homogenates as well as extracted mitochondria and microsomes of rats 28 hr after treatment with an LD70–90 dose of endotoxin. Experiments were also conducted with in vitro incubation of rat hepatic lysosomes for various times and various concentrations of endotoxin. The results of these experiments show no significant difference from control values of the various phospholipids analyzed subsequent to endotoxin treatment. It must be concluded on the basis of these experiments that the damage observed biochemically and by electron microscopy is related to some cause other than the membranolytic effect of lysophosphatides.