Helicobacter pylori-induced activation of human endothelial cells.
Helicobacter pylori infection causes active chronic inflammation with a continuous recruitment of neutrophils to the inflamed gastric mucosa. To evaluate the role of endothelial cells in this process, we have examined adhesion molecule expression and chemokine and cytokine production from human umbilical vein endothelial cells stimulated with well-characterized H. pylori strains as well as purified proteins. Our results indicate that endothelial cells actively contribute to neutrophil recruitment, since stimulation with H. pylori bacteria induced upregulation of the adhesion molecules VCAM-1, ICAM-1, and E-selectin as well as the chemokines interleukin 8 (IL-8) and growth-related oncogene alpha (GRO-alpha) and the cytokine IL-6. However, there were large variations in the ability of the different H. pylori strains to stimulate endothelial cells. These interstrain variations were seen irrespective of whether the strains had been isolated from patients with duodenal ulcer disease or asymptomatic carriers and were not solely related to the expression of known virulence factors, such as the cytotoxin-associated gene pathogenicity island, vacuolating toxin A, and Lewis blood group antigens. In addition, one or several unidentified proteins which act via NF-kappaB activation seem to induce endothelial cell activation. In conclusion, human endothelial cells produce neutrophil-recruiting factors and show increased adhesion molecule expression after stimulation with certain H. pylori strains. These effects probably contribute to the continuous recruitment of neutrophils to H. pylori-infected gastric mucosa and may also contribute to tissue damage and ulcer formation.
Department of Medical Microbiology and Immunology, Sahlgrenska Academy at Göteborg University, Sweden. mikael.innocenti@rheuma.gu.se
M
M
Innocenti
A-C
AC
Thoreson
R L
RL
Ferrero
E
E
Strömberg
I
I
Bölin
L
L
Eriksson
A-M
AM
Svennerholm
M
M
Quiding-Järbrink
D000328:Adult; D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000276:immunology; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000096:biosynthesis; D054360:Chemokine CXCL1; D054357:Chemokine CXCL10; D019743:Chemokines, CXC / Q000096:biosynthesis; D002630:Chemotactic Factors / Q000096:biosynthesis; D019040:E-Selectin / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006133:Growth Substances / Q000096:biosynthesis; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D001426:Bacterial Proteins; C475829:CXCL1 protein, human; D018946:Chemokine CCL5; D054360:Chemokine CXCL1; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D019040:E-Selectin; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D016178:Granulocyte-Macrophage Colony-Stimulating Factor