Relationship of chemical structure to pathophysiologic properties of endotoxin from Serratia marcescens

Prior investigations in a variety of animal species have demonstrated clearly that endotoxin administration is capable of eliciting a notable series of pathophysiologic events culminating in irreversible shock and death. Results from out previous studies have implicated the lipopolysaccharide portion of the endotoxin moiety as the responsible agent for these events. The present work was carried out to define more precisely the chemical nature of the active site of the endotoxin. Endotoxin from Serratia marcescens has been degraded by aqueous phenol or acetic acid hydrolysis into a number of chemically defined structural fragments. Intravenous injections of these fragments into unanesthetized or anesthetized animals was carried out to compare their biochemical, hemodynamic, and lethality relationships. Results suggest strongly that the typical pathophysiologic manifestations of endotoxin shock depend on the presence of ester linked fatty acids in the lipid moiety of the endotoxin complex.