A novel lipid A fromHalomonas magadiensis inhibits enteric LPS-induced human monocyte activation

Ialenti, A., Di Meglio, P., Grassia, G., Maffia, P. , Di Rosa, M., Lanzetta, R., Molinaro, A., Silipo, A., Grant, W. and Ianaro, A. (2006) A novel lipid A fromHalomonas magadiensis inhibits enteric LPS-induced human monocyte activation. European Journal of Immunology, 36(2), pp. 354-360. (doi: 10.1002/eji.200535305) (PMID:16365914)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Maffia, Professor Pasquale and Grassia, Dr Gianluca
• Authors: Ialenti, A., Di Meglio, P., Grassia, G., Maffia, P., Di Rosa, M., Lanzetta, R., Molinaro, A., Silipo, A., Grant, W., and Ianaro, A.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: European Journal of Immunology
• Publisher: Wiley
• ISSN: 0014-2980
• ISSN (Online): 1521-4141