Mechanisms involved in Helicobacter pylori-induced inflammation
N Yoshida1, D N Granger, D J Evans
1Department of Physiology, Louisiana State University Medical Center, Shreveport.
Background:
Helicobacter pylori infection is associated with mucosal inflammation. The aims of the present study were to assess whether a water extract of H. pylori promotes neutrophil (polymorphonuclear leukocyte [PMN]) adherence to endothelial cells and define the molecular basis of this adhesive interaction.
Methods:
Intravital microscopy was used to study leukocyte adhesive interactions in rat mesenteric venules in situ. PMN-endothelial cell adhesive interactions were studied in vitro using human PMNs and monolayers of human umbilical vein endothelial cells (HUVEC).
Results:
In vivo, superfusion of rat mesentery with the H. pylori extract increased leukocyte adhesion and emigration in venules. In vitro, adhesion of human PMNs to HUVEC was increased by the H. pylori extract in a concentration-dependent manner. Pretreatment of HUVEC alone with H. pylori extract had no effect on PMN adherence, whereas pretreatment of PMN alone significantly increased their adherence to HUVEC. The extract-induced adhesion was significantly diminished by monoclonal antibodies (MAb) directed against either CD11a, CD11b, or CD18 on neutrophils, and by MAbs against intercellular adhesion molecule-1 (ICAM-1), but not E- or P-selectin, on endothelial cells.
Conclusions:
These studies suggest that products of H. pylori elicit gastrointestinal inflammation by promoting PMN adhesion to endothelial cells via CD11a/CD18- and CD11b/CD18-dependent interactions with ICAM-1.
Insights
Helicobacter pylori extracts promote neutrophil adhesion to endothelial cells, driving gastrointestinal inflammation through ICAM-1 interactions. This study clarifies a key mechanism in H. pylori-induced inflammation.
Area of Science:
- Gastroenterology
- Immunology
- Microbiology
Background:
- Helicobacter pylori infection is a known cause of gastrointestinal mucosal inflammation.
- Understanding the molecular mechanisms of H. pylori-induced inflammation is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate if a water extract of H. pylori enhances neutrophil (polymorphonuclear leukocyte [PMN]) adherence to endothelial cells.
- To elucidate the molecular pathways involved in this PMN-endothelial cell adhesive interaction.
Main Methods:
- Intravital microscopy was employed to observe leukocyte adhesion and emigration in rat mesenteric venules in vivo.
- In vitro studies utilized human PMNs and human umbilical vein endothelial cells (HUVEC) to assess PMN-endothelial cell adhesion.
Main Results:
- H. pylori extract increased leukocyte adhesion and emigration in vivo.
- In vitro, the extract dose-dependently enhanced PMN adherence to HUVEC, primarily by affecting PMNs.
- This adhesion was mediated by neutrophil CD11a/CD18 and CD11b/CD18 interactions with endothelial ICAM-1, but not selectins.
Conclusions:
- H. pylori products contribute to gastrointestinal inflammation by increasing PMN adhesion to endothelial cells.
- The interaction involves specific adhesion molecules: CD11a/CD18 and CD11b/CD18 on PMNs binding to ICAM-1 on endothelial cells.
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