A novel lipid A from Halomonas magadiensis inhibits enteric LPS‐induced human monocyte activation

Lipopolysaccharide (LPS) endotoxin is the bacterial product responsible for the clinical syndrome of Gram‐negative septicemia and endotoxic shock. During sepsis, microbial antigens, such as LPS, activate monocytes and macrophages to produce several pro‐inflammatory cytokines, among which tumor necrosis factor‐α (TNF‐α) appears to be very important for the development of endotoxic shock. The endotoxic properties of LPS principally reside in the lipid A (LIP A) component, which is the primary immunostimulatory center of Gram‐negative bacteria. In recent years there has been a continuous effort to identify molecules able to antagonize the deleterious effects of endotoxic shock. In this study we show that a novel LIP A fraction from the LPS of Halomonas magadiensis (Hm), a Gram‐negative extremophilic and alkaliphilic bacterium, significantly inhibits the synthesis of TNF‐α by human monocytes activated by Escherichia coli LPS. LIP A from Hm exerts these effects by interfering with E. coli LPS for activation of Toll‐like receptor 4 expressed in human cells. This result defines Hm LIP A as a novel class of LPS antagonist whose structural features could be utilized for the design of compounds for the treatment of Gram‐negative sepsis.