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 proinflammatory cytokines, among which tumor necrosis factor-a (TNF-alpha) 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 xtremophilic and alkaliphilic bacterium, significantly inhibits the synthesis of TNF-alpha 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.
A novel lipid A from Halomonas magadiensis inhibits enteric LPS-induced human monocyte activation / Ialenti, Armando; P., Di Meglio; Grassia, Gianluca; Maffia, Pasquale; M., Di Rosa; Lanzetta, Rosa; Molinaro, Antonio; Silipo, Alba; W., Grant; Ianaro, Angela. - In: EUROPEAN JOURNAL OF IMMUNOLOGY. - ISSN 0014-2980. - ELETTRONICO. - 36:(2006), pp. 354-360.
A novel lipid A from Halomonas magadiensis inhibits enteric LPS-induced human monocyte activation
IALENTI, ARMANDO;GRASSIA, GIANLUCA;MAFFIA, PASQUALE;LANZETTA, ROSA;MOLINARO, ANTONIO;SILIPO, ALBA;IANARO, ANGELA
2006
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 proinflammatory cytokines, among which tumor necrosis factor-a (TNF-alpha) 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 xtremophilic and alkaliphilic bacterium, significantly inhibits the synthesis of TNF-alpha 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.