Effects of iron on bacterial endotoxin

Abstract

Bacterial endotoxin, a major modulator of morbidity and mortality during bacterial sepsis, has affinity for cations. Binding of certain cations to LPS can cause alterations of LPS size and ultrastructure, and can affect LPS biological potency. Although the addition of iron to LPS has been shown previously to result in decreased LPSmediated lethality in mice, it is not certain whether this represents a direct effect of iron on LPS biological activity. To examine this possibility, we measured binding of ferrous or ferric iron to Escherichia coli LPS in vitro. 1.5-2 moles of iron (regardless of oxidation state) was shown to bind per mole LPS. Binding of iron to LPS produced a dose-dependent decrease in two measures of LPS biological activity, activation of Limulus amebocyte lysate (which decreased to 10% of control when LPS was saturated with Fe) and stimulation of endothelial cell procoagulant activity (which decreased to 1-10% of control when LPS was saturated with Fe).