Am J Physiol Cell Physiol AJP: Heart and Circulatory Physiology
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Am J Physiol Cell Physiol 293: C1788-C1796, 2007. First published September 13, 2007; doi:10.1152/ajpcell.00141.2007
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GROWTH, DIFFERENTIATION, AND APOPTOSIS

C/EBPβ phosphorylation rescues macrophage dysfunction and apoptosis induced by anthrax lethal toxin

Martina Buck and Mario Chojkier

Department of Medicine, University of California, and Veterans Affairs Healthcare System, San Diego, California

Submitted 4 April 2007 ; accepted in final form 10 September 2007

Bacillus anthracis lethal toxin (LT) impairs innate and adaptive immunity. Anthrax lethal factor stimulates cleavage of MAPK kinases, which prevents the activation of antiapoptotic MAPK targets. However, these MAPK targets have not been yet identified. Here, we found that LT induces macrophage apoptosis by enhancing caspase 8 activation and by preventing the activation of ribosomal S6 kinase-2 (RSK), a MAPK target, and the phosphorylation of CCAAT/enhancer binding protein-β (C/EBPβ) on T217, a RSK target. Expression of the dominant positive, phosphorylation mimic C/EBPβ-E217 rescued macrophages from LT-induced apoptosis by blocking the activation of procaspase 8. LT inhibited macrophage phagocytosis and oxidative burst and induced apoptosis in normal mice but not in C/EBPβ-E217 transgenic mice. These findings suggest that C/EBPβ may play a critical role in anthrax pathogenesis, at least in macrophages.

apoptosis; macrophages; mitogen-associated protein kinase; ribosomal S6 kinase-2


Address for reprint requests and other correspondence: M. Buck, Dept. of Medicine, Univ. of California-San Diego, and Veterans Affairs Healthcare System, San Diego, CA 92161 (e-mail: mbuck{at}ucsd.edu)






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