Selective Upregulation of Endothelial E-Selectin in Response toHelicobacter pylori-Induced Gastritis

Abstract

Helicobacter pylori is one of the most common bacterial pathogens, infecting up to 50% of the world's population. The host is not able to clear the infection, leading to life-long chronic inflammation with continuous infiltration of lymphocytes and granulocytes. The migration of leukocytes from the blood into inflamed tissue is dependent on adhesion molecules expressed on the vascular endothelium. The aim of this study was to characterize the effect of H. pylori-induced gastritis with regard to the expression of endothelial adhesion molecules in the gastric mucosa and compare this to other types of chronic mucosal inflammations. Our results demonstrate an increased level of expression of the adhesion molecule E-selectin, but not of intracellular adhesion molecule 1, vascular adhesion molecule 1, or vascular adhesion protein 1, in H. pylori-induced gastritis but not in gastritis induced by acetylsalicylic acid or pouchitis. The upregulated E-selectin expression was determined to be localized to the gastric mucosa rather than being a systemic response to the infection. Moreover, the H. pylori type IV secretion system encoded by the cag pathogenicity island (cagPAI) was found to be an important determinant for the upregulation of human endothelial E-selectin expression in vitro, and this process is probably dependent on the CagL protein, mediating binding to ␣5␤1 integrins. Thus, endothelial E-selectin expression induced by H. pylori probably contributes to the large influx of neutrophils and macrophages seen in infected individuals, and our results suggest that this process may be more pronounced in patients infected with cagPAI-positive H. pylori strains and may thereby contribute to tissue damage in these individuals.

Targeting peripheral opioid receptors to promote analgesic and anti-inflammatory actions

“…The homing of leukocytes to inflamed tissues involves a precise series of events which begin with circulating leukocytes tethering to and rolling along the vascular endothelial cell wall in a process mediated by P-, E-, and L-selectins (Koning et al, 2002; Stein et al, 2003; Figure 1 ). Upregulation of these cell adhesion molecules has been noted in many models of inflammation (Schurmann et al, 1995; Krishna et al, 1997; Navarro et al, 2002; Almulki et al, 2009; Svensson et al, 2009). Leukocytes are then activated by chemokines released from inflammatory cells and presented on the luminal surface of the endothelium (Koning et al, 2002; Machelska et al, 2002; Stein et al, 2003).…”

Helicobacter pylori interferes with leukocyte migration via the outer membrane protein HopQ and via CagA translocation

“…Apart from dendritic cells migrating towards the lymph nodes, neutrophils are recruited to the gastric submucosa via chemotaxis towards CXCL1-3 (GRO␣, ␤ and ␥) and CXCL8 (IL-8) (Yamaoka et al, 1998), and via endothelial cell activation characterized by upregulation of E-selectin, VCAM-1 and ICAM-1 (Innocenti et al, 2002;Svensson et al, 2009). Moreover, the bacterial protein HP-NAP (H. pylori neutrophil-activating protein) has been shown to attract and to activate neutrophils (Evans et al, 1995;Polenghi et al, 2007;Satin et al, 2000).…”

The homing receptor CD44 is involved in the progression of precancerous gastric lesions in patients infected with Helicobacter pylori and in development of mucous metaplasia in mice

“…The inflammatory process, in general, involves cellular activation, migration, and infiltration into the inflamed site through the interaction between cellular receptors and ligands on the endothelium (reviewed in[19]). Selectins are major endothelial ligands induced in response to inflammation [20], and of these, E-selectins seem to be especially induced by H. pylori infection [21]. CD44, a cell-adhesion molecule expressed on a great variety of cell types including leukocytes and epithelial cells, has been shown to participate in the migration of inflammatory cells [22–26].…”