Influence of Altered Reticuloendothelial Function on Vascular Clearance and Tissue Distribution of S. enteritidis Endotoxin 1

Summary

In an attempt to define the mechanism by which the reticuloendothelial stimulant, glucan, profoundly enhances susceptibility and conversely that the RES depressant, methyl palmitate, produces a resistance to intravenously administered endotoxins, the vascular clearance and tissue distribution of intravenously administered ⁵¹Crlabeled S. enteritidis endotoxin were studied. The vascular clearance of the labeled endotoxin preparation was biphasic consisting of an early, or fast, component followed by a slow component. The RES stimulant, glucan, enhanced both phases of removal and produced a significant increase in the hepatic localization of the endotoxin. Splenic and lung uptake were unaltered. In contrast, methyl palmitate exerted no influence on the vascular removal rate of endotoxin, but induced a significant decrease in splenic uptake. The administration of heparin, which has been previously demonstrated to modify endotoxin lethality, decreased the early phase of vascular clearance, but did not modify the tissue localization pattern. These studies dissociate the vascular clearance and tissue distribution of endotoxin from previously reported alterations in endotoxin lethality. The importance of a cellular-mediated response to endotoxemia as a major determinant to endotoxin induced lethality is suggested.