ABSTRACT
Helicobacter pylori-associated gastritis (HAG) is characterized by granulocytic and mononuclear cell infiltrates within infected gastric mucosa. Since the bacterium does not invade the epithelial layer, it must be assumed that components or products of the pathogen which permeate the epithelial barrier may initiate chemotaxis and activation of neutrophils. The aim of this study was to evaluate the effect of H. pylori water soluble protein (WSP) components on the induction of granulocyte adherence and activation. The results show that H. pylori WSP led to enhanced expression of the beta 2-integrin CD11b/CD18 on the granulocyte surface. Following upregulation of this adhesion molecule, activated granulocytes demonstrated increased adhesion to human endothelial cells (HUVEC) in culture. These observations support the hypothesis that in vivo neutrophil activation may be a direct result of H. pylori constituents promoting transendothelial migration into the lamina propria of infected gastric mucosa.
Subject(s)
Endothelium, Vascular/physiology , Granulocytes/physiology , Helicobacter pylori/physiology , Bacterial Proteins/physiology , CD18 Antigens/biosynthesis , Cell Adhesion , Cells, Cultured , Chemotaxis, Leukocyte , Endothelium, Vascular/microbiology , Flow Cytometry/methods , Granulocytes/microbiology , Humans , Macrophage-1 Antigen/biosynthesis , Models, Biological , Umbilical VeinsABSTRACT
Type B gastritis in its active form is characterized by a dense infiltration of the lamina propria with granulocytes. Since the bacterium Helicobacter pylori does not invade the epithelial barrier, a signaling pathway chemoattractive for granulocytes must exist across this mucosal boarder. One possible mechanism tested was whether granulocytes are directly activated by water-soluble membrane proteins (WSP) from H. pylori. These findings were compared with the effects of WSP from other bacteria (Helicobacter felis, Campylobacter jejuni, Escherichia coli, and Staphylococcus aureus). A unique activation pattern by H. pylori WSP was found. Like all other WSP tested, they induced an upregulation of CD11b but had no influence on CD11c and, most strikingly, CD62L expression. In contrast, E. coli WSP, e.g., not only induce a strong CD11b and CD11c expression but also lead to a loss in surface CD62L. The lack of CD62L shedding conserves rolling of granulocytes along the endothelium, creating a favorable precondition for granulocytes to stick more readily to activated endothelium after H. pylori stimulation via CD11b-CD54 receptor-counterreceptor interaction. This may explain why H. pylori infection is a very strong stimulus for granulocyte infiltration. The active fraction for the induction of CD11b on granulocytes is a heat- and protease-sensitive protein with a molecular mass between 30 and 100 kDa. One activation step involved may be the binding of WSP to CD15 determinants on granulocytes with subsequent induction of CD11b.
