Bartonella henselae inhibits apoptosis in Mono Mac 6 cells.
Bartonella henselae causes the vasculoproliferative disorders bacillary angiomatosis and peliosis probably resulting from the release of vasculoendothelial growth factor (VEGF) from infected epithelial or monocytic host cells. Here we demonstrate that B. henselae in addition to VEGF induction was also capable of inhibiting the endogenous sucide programme of monocytic host cells. Our results show that B. henselae inhibits pyrrolidine dithiocarbamate (PDTC)-induced apoptosis in Mono Mac 6 cells. B. henselae was observed to be present in a vacuolic compartment of Mono Mac 6 cells. Direct contact of B. henselae with Mono Mac 6 cells was crucial for inhibition of apoptosis as shown by the use of a two-chamber model. Inhibition of apoptosis was paralleled by diminished caspase-3 activity which was significantly reduced in PDTC-stimulated and B. henselae-infected cells. The anti-apoptotic effect of B. henselae was accompanied by (i) the activation of the transcription factor NF-kappaB and (ii) the induction of cellular inhibitor of apoptosis proteins-1 and -2 (cIAP-1, -2). Our results suggest a new synergistic mechanism in B. henselae pathogenicity by (i) inhibition of host cell apoptosis via activation of NF-kappaB and (ii) induction of host cell VEGF secretion.
Kempf
Volkhard A J
VA
Institut für Medizinische Mikrobiologie und Hygiene, Eberhard-Karls-Universität, Tübingen, Germany. volkhard.kempf@med.uni-tuebingen.de
Schairer
Annette
A
Neumann
Diana
D
Grassl
Guntram A
GA
Lauber
Kirsten
K
Lebiedziejewski
Maria
M
Schaller
Martin
M
Kyme
Pierre
P
Wesselborg
Sebastian
S
Autenrieth
Ingo B
IB
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D018416:Bartonella henselae / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D002460:Cell Line; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D009000:Monocytes / Q000382:microbiology* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D014617:Vacuoles / Q000382:microbiology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000975:Antioxidants; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D011506:Proteins; D011759:Pyrrolidines; D013859:Thiocarbamates; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C020972:pyrrolidine dithiocarbamic acid; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases