Activation of Histamine-Releasing Factor in Normal Rat Plasma by E. coli Endotoxin

Abstract

Summary

Employing isolated guinea pig ileum segments in aerated Tyrode solution, 5 to 250 μg aliquots of a physiologically active lipopolysaccharide component of E. coli endotoxin were found capable of activating a potent histamine-like releasing factor upon in vitro incubation with 0.5 ml diluted fresh heparinized normal rat plasma. The release of histamine by this rat plasma factor occurred within seconds after tissue contact. The E. coli endotoxin preparation per se, in the dose-time relations employed, did not liberate histamine directly from the ileum segments; indeed, 2000 μg E. coli endotoxin failed to release detectable histamine during 20 minute tissue contact periods. This lack of histamine-releasing activity could not be attributed to preexisting endotoxin contamination of the tissue bath nor to toxic depression of the histamine sensitivity of the assay system. The above findings, in conjunction with previous evidence, suggest that E. coli lipopolysaccharide behaves, at least in one manner, as do numerous other high molecular weight polysaccharides and justifies the hypothesis that activation of plasma histamine-releasing factors may account for certain of the pathophysiologic alterations which characterize the endotoxic response. Further studies are required to define the importance of the polysaccharide moiety of the endotoxin molecule for the histamine-releasing activity.