Effect of Bacillus anthracis lethal toxin on human peripheral blood mononuclear cells

FEBS Letters

Popov, Serguei G¹  Bailey, Charles¹  Grene, Edith¹  Villasmil, Rafael¹  Alibek, Darya¹  Bernardi, Jessica¹  Wu, Aiguo¹  Cardwell, Jennifer¹  Popova, Taissia¹  Alibek, Ken¹ 

[1] Advanced Biosystems, Inc., 10900 University Blvd., MSN 1A8, Manassas, VA 20110, USA

关键词: Anthrax;    Apoptosis;    Bactericidal activity;    Lethal toxin;    Peripheral blood;    Mononuclear cell;    LF;    lethal factor;    PA;    protective antigen;    LeTx;    lethal toxin;    CW;    Bacillus anthracis cell wall preparation;    MAPKK;    mitogen-activated protein kinase kinase;    PBMC;    human peripheral blood mononuclear cells;    AM;    activated monocytes;   

DOI  :  10.1016/S0014-5793(02)03228-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Lethal toxin (LeTx) plays a central role in anthrax pathogenesis, however a cytotoxicity of LeTx has been difficult to demonstrate in vitro. No cytolytic effect has been reported for human cells, in contrast to murine cell lines, indicating that cell lysis can not be considered as a marker of LeTx activity. We have recently shown that murine macrophage-like RAW 264.7 cells treated with LeTx or infected with anthrax spores underwent changes typical of apoptotic death. Here we demonstrate that cells from human peripheral blood display a proapoptotic behavior similar to murine cells. TUNEL assay detected a nucleosomal degradation typical of apoptosis in peripheral blood mononuclear cells (PBMC) treated with LeTx. Membrane staining with apoptotic dyes was detected in macrophages derived from monocytes in presence of LeTx. The toxin inhibited production of proinflammatory cytokines in PBMC stimulated with a preparation of Bacillus anthracis cell wall. Infection of PBMC with anthrax spores led to the appearance of a large population of cells stained positively for apoptosis, with a reduced capacity to eliminate spores and vegetative bacteria. The aminopeptidase inhibitor, bestatin, capable of protecting cells from LeTx, restored a bactericidal activity of infected cells. These findings may be explained by LeTx expression within phagocytes and support an important role of LeTx as an early intracellular virulence factor contributing to bacterial dissemination and disease progression.

【 授权许可】

Unknown