NDLI: Bartonella-associated endothelial proliferation depends on inhibition of apoptosis.

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Bartonella-associated endothelial proliferation depends on inhibition of apoptosis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Nekorchuk, Dawn M. Kirby, James E.
Description	Author Affiliation: Kirby JE ( Department of Pathology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, RN270G, Boston, MA 02215, USA. jekirby@caregroup.harvard.edu);
Abstract	Bartonella is a Gram-negative pathogen that is unique among bacteria in being able to induce angioproliferative lesions. Cultured human endothelial cells have provided an in vitro system in which to study the basis of angioproliferation. Previous studies have attributed the organism's ability to induce angioproliferative lesions to direct mitotic stimulation of endothelial cells by these bacteria. Here we show that Bartonella inhibits apoptosis of endothelial cells in vitro, and that its ability to stimulate proliferation of endothelial cells depends to a large extent on its antiapoptotic activity. Bartonella suppresses both early and late events in apoptosis, namely caspase activation and DNA fragmentation, respectively. Its ability to inhibit death of endothelial cells after serum starvation can be recapitulated by media conditioned by bacteria, indicating that direct cell contact is not necessary. Among tested strains, the activity is produced only by Bartonella species that are significant human pathogens and are associated with angioproliferative lesions. We suggest that endothelial cells normally respond to infection by undergoing apoptosis and that Bartonella evolved the antiapoptotic activity to enhance survival of the host cells and therefore itself. We propose that Bartonella's antiapoptotic mechanism accounts at least in part for its ability to induce vascular proliferation in vivo.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	7
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Apoptosis Bartonella Physiology Endothelium, Vascular Cytology Amino Acid Chloromethyl Ketones Pharmacology Animals Cell Division Cell Line Culture Media, Conditioned Mitosis Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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