Effect of Helicobacter pylori Lipopolysaccharide (LPS) and LPS Derivatives on the Production of Tissue Factor and Plasminogen Activator Inhibitor Type 2 by Human Blood Mononuclear Cells

Abstract

Different Helicobacter pylori lipopolysaccharides (LPSs) and LPS-derivatives were studied for their ability to induce the production of procoagulant activity (PCA) and plasminogen activator inhibitor type 2 (PAI-2) by human blood mononuclear leukocytes. Smooth (S)- and rough (R)-form LPSs caused a similar increase in cell-associated PCA (tissue factor) and PAI-2 antigen release. Both effects were potentiated by fetal bovine serum via a CD14-mediated mechanism. The potency of H. pylori LPSs was approximately 1000-fold lower than that of Salmonella typhimurium LPSs. When H. pylori LPS derivatives (dephosphorylated R-LPS, S-lipid A, and R-lipid A) were used, PCA and PAI-2 production were markedly reduced. R-lipid A was approximately 4-fold less efficient than S-lipid A. These findings suggest that the induction of monocyte tissue factor and PAI-2 by H. pylori LPS is influenced by the lipid A structure and modulated by the core oligosaccharide and that phosphate groups present in both regions may play an important role.

Helicobacter pyloriInduces Plasminogen Activator Inhibitor 2 in Gastric Epithelial Cells through Nuclear Factor-κB and RhoA

“…24,35). In part, the increase has been attributable to the effect of lipopolysaccharide, although H. pylori lipopolysaccharide is a relatively weak inducer of PAI-2 in mononuclear cells compared with other bacteria (35,36).…”

“…24,35). In part, the increase has been attributable to the effect of lipopolysaccharide, although H. pylori lipopolysaccharide is a relatively weak inducer of PAI-2 in mononuclear cells compared with other bacteria (35,36). In addition, other virulence factors, including H. pylori neutrophil-activating protein, have been reported to induce PAI-2 in mononuclear cells (24).…”

Lipopolysaccharide in bacterial chronic infection: Insights from Helicobacter pylori lipopolysaccharide and lipid A

“…For instance, the phosphorylation pattern in lipid A has been shown to influence cytokine production and induction of procoagulant activity from mononuclear leukocytes, and Limulus amoebocyte activity, but the core OS modulated some of these effects (Pece et al, 1995;Semeraro et al, 1996). On the other hand, the phosphorylation pattern of H. pylori lipid A was of lesser importance than acylation pattern in priming neutrophils for toxic oxygen radical release (Nielsen et al, 1994), and the lack of abolition of suppressor T-cell activity has been attributed to the presence of long-chain fatty acids in H. pylori lipid A (Baker et al, 1994).…”

“…Whether during long-term chronic infection of the gut mucosa by H. pylori, low-grade LPS/lipid A stimuli contribute to such extragastric infection sequelae is a tantalizing question (Moran, 1999;Grebowska et al, 2006). The structural prerequisites for low-grade expression of tissue factor (leading to fibrin formation) and plasminogen activator inhibitor type 2 (leading to persistence of the formed fibrin) by monocytes are present within H. pylori LPS (Semeraro et al, 1996). Moreover, H. pylori LPS has been shown to be capable of inducing a microvascular inflammatory response in cardiac, renal, hepatic and pulmonary tissues mediated by inducible nitric oxide synthase and to produce a vasomotor effect on isolated rabbit aorta (Hynes et al, 2003).…”

The role of Helicobacter pylori LPS in the pathogenesis of H. pylori-related gastropathy

“…In this scenario, it has been hypothesized that, by exocytosis, macrophages of the gastric mucosa may release LPS degradative products which behave as prolonged subliminal stimuli able to trigger the release of pro-inflammatory cytokines, which, in turn, could contribute to gastric mucosa damage in H. pylori related gastropathy. 5,6 Gastric mucosa growth factors and cytokines in H. pylori-infected patients The exact mechanisms by which H. pylori cells damage gastric mucosa are not well understood, mostly because of the complexity of bacterial constituents which include cytotoxins (CagA and VacA), urease, and LPSs, all endowed with toxic effects in the host. The best evidence for the harmful effects of the bacterium within the gastric mucosa is provided by studies conducted on gastric mucosal biopsy specimens collected from H. pyloriinfected patients before and after successful eradicating treatment.…”