Extract of Helicobacter pylori induces neutrophils to injure endothelial cells and contains antielastase activity.
OBJECTIVE
Previous studies indicate that a water extract of Helicobacter pylori promotes leukocyte adhesion and emigration as well as endothelial barrier disruption (increased vascular protein leakage) in rat mesenteric venules. The aims of this study were to assess whether H. pylori extract-activated neutrophils disrupt endothelial cell monolayers and to identify the mechanisms involved in this process.


METHODS
Human neutrophils were incubated with monolayers of human umbilical vein endothelial cells (HUVECs) in the presence or absence of H. pylori extract.


RESULTS
H. pylori extract-activated human neutrophils produced endothelial cell detachment from HUVEC monolayers, the severity of which was dependent on the duration of exposure. Endothelial cell detachment was prevented by a monoclonal antibody directed against CD11/CD18 on neutrophils or a monoclonal antibody against intercellular adhesion molecule 1 on endothelial cells. HUVEC monolayer disruption was also prevented by superoxide dismutase, catalase, and a monoclonal antibody against elastase. Further studies indicated that H. pylori extract was capable of inhibiting human neutrophil elastase. The antielastase activity was not diminished by oxidants.


CONCLUSIONS
These studies indicate that H. pylori extract-activated human neutrophils can disrupt HUVEC monolayers only when human neutrophils are allowed to adhere to HUVECs and may provide an explanation for the H. pylori extract-induced, neutrophil-dependent vascular protein leakage observed in vivo. The possibility that H. pylori releases antiproteases may explain, in part, why this bacterium is so virulent.
Department of Physiology, Louisiana State University Medical Center, Shreveport, USA.
T
T
Takemura
D N
DN
Granger
D J
DJ
Evans
D G
DG
Evans
D Y
DY
Graham
D C
DC
Anderson
R E
RE
Wolf
G
G
Cepinskas
P R
PR
Kvietys
D000911:Antibodies, Monoclonal; D002374:Catalase / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D004730:Endothelium, Vascular / Q000473:pathology*; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D006997:Hypochlorous Acid / Q000494:pharmacology; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors*; D009504:Neutrophils / Q000502:physiology*; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D013482:Superoxide Dismutase / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D003470:Culture Media; D006997:Hypochlorous Acid; D002374:Catalase; D013482:Superoxide Dismutase; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase