Human polymorphonuclear leukocytes are sensitive in vitro to Helicobacter pylori vaca toxin.
BACKGROUND
Interactions between bacterial components and polymorphonuclear leukocytes (PMNL) play a major pathogenic role in Helicobacter pylori-associated diseases. Activation of PMNL can be induced by contact with whole bacteria or by different H. pylori products released in the extracellular space either by active secretion or by bacterial autolysis. Among these products, H. pylori VacA is a secreted toxin inducing vacuolation and apoptosis of epithelial cells.


RESULTS
We found that non-opsonic human PMNL were sensitive to the vacuolating effect of VacA+ broth culture filtrate (BCF) and of purified VacA toxin. PMNL incubated with VacA+ BCF showed Rab7-positive large intracytoplasmic vacuoles. PMNL preincubation with H. pylori BCF of different phenotypes dramatically potentialized the oxidative burst induced by zymosan, increased phagocytosis of opsonized fluorescent beads, and up-regulated CD11b cell surface expression, but independently of the BCF VacA phenotype. Moreover, by using purified VacA toxin we showed that vacuolation induced in PMNL did not modify the rate of spontaneous PMNL apoptosis measured by caspase 3 activity.


CONCLUSIONS
Taken together, these data showed that human PMNL is a sensitive cell population to H. pylori VacA toxin. However, activation of PMNL (i.e., oxidative burst, phagocytosis, CD11b up-regulation) and PMNL apoptosis are not affected by VacA, raising question about the role of VacA toxin on PMNL in vivo.
Brest
Patrick
P
INSERM ERI-21, Pasteur'Hospital and Faculty of Medicine, University of Nice, Nice, France.
Hofman
Véronique
V
Lassalle
Sandra
S
Césaro
Annabelle
A
Ricci
Vittorio
V
Selva
Eric
E
Auberger
Patrick
P
Hofman
Paul
P
D017209:Apoptosis; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D017077:Culture Media, Conditioned / Q000378:metabolism; D016480:Helicobacter pylori / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis; D016897:Respiratory Burst; D014617:Vacuoles / Q000378:metabolism / Q000648:ultrastructure; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
D001426:Bacterial Proteins; D039481:CD11b Antigen; D017077:Culture Media, Conditioned; C074689:VacA protein, Helicobacter pylori; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D020691:rab GTP-Binding Proteins