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Infection and Immunity, June 2004, p. 3260-3266, Vol. 72, No. 6
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.6.3260-3266.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Lipopolysaccharide Protects Primary B Lymphocytes from Apoptosis by Preventing Mitochondrial Dysfunction and Bax Translocation to Mitochondria

Vongthip Souvannavong,1* Christophe Lemaire,2 and Richard Chaby1

Equipe Endotoxines, UMR 8619 CNRS-UPS, Université de Paris-Sud, 91405 Orsay Cedex,1 Equipe Biochimie de l'Apoptose, CNRS FRE 2445, Université de Versailles/St. Quentin, 78035 Versailles, France2

Received 8 September 2003/ Returned for modification 22 December 2003/ Accepted 28 January 2004

Mature B lymphocytes undergo apoptosis when they are cultured in the absence of survival factors. Gram-negative bacterial lipopolysaccharide (LPS) prevents this spontaneous apoptosis. This study aimed to better define the signaling pathway(s) involved in the antiapoptotic activity of this endotoxin. We report here that, in addition to its effects on spontaneous apoptosis, LPS protects B cells from apoptosis induced by the broad-spectrum protein kinase inhibitor staurosporine. LPS increased cell viability and concomitantly maintained the mitochondrial transmembrane potential ({Delta}{Psi}m) and high glutathione levels. Moreover, LPS inhibited cytosolic cytochrome c release and decreased caspase-9 activation. Unlike staurosporine, LPS induced the retention of Bax, a proapoptotic protein of the Bcl-2 family, in the cytosol by preventing its translocation to mitochondria. These results suggest that Bax relocalization from the cytosol to the mitochondria is an important step of mature B-cell apoptosis and that the antiapoptotic activity of LPS occurs upstream of mitochondrial events.

* Corresponding author. Mailing address: Equipe Endotoxines, UMR 8619 CNRS-UPS, Université de Paris-Sud, BÂtiment 430, 91405 Orsay cedex, France. Phone: 33-1 69 15 48 45. Fax: 33-1 69 85 37 15. E-mail: vongthip.souvannavong{at}bbmpc.u-psud.fr.

Editor: A. D. O'Brien

Infection and Immunity, June 2004, p. 3260-3266, Vol. 72, No. 6
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.6.3260-3266.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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