Document Detail

Shigella-induced necrosis and apoptosis of U937 cells and J774 macrophages.
MedLine Citation:
PMID:  12949176     Owner:  NLM     Status:  MEDLINE    
It is currently unclear whether Shigella kills its phagocytic host cells by apoptosis or necrosis. This study shows that rapid necrosis ensues in macrophage-like cell lines (U937 cells differentiated by all-trans-retinoic acid and J774 cells) infected with the Shigella flexneri strain YSH6000. The infected cells rapidly lose membrane integrity, a typical feature of necrosis, as indicated by the release of the cytoplasmic lactate dehydrogenase and the exposure of phosphatidylserine (PS) associated with the rapid uptake of propidium iodide (PI). The infected cells exhibit DNA fragmentation without nuclear condensation, and substantial involvement of either caspase-3/-7 or caspase-1 was not detected, which is also contrary to what is normally observed in apoptosis. Cytochalasin D potently inhibited Shigella-induced cell death, indicating that only internalized Shigella can cause necrosis. Osmoprotectants such as polyethylene glycols could suppress cell death, suggesting that insertion of a pore by Shigella into the host cell membrane induces the necrosis. The pore was estimated to be 2.87+/-0.4 nm in diameter. Shigella was also found to be able to induce apoptosis but only in one of the lines tested and under specific conditions, namely U937 cells differentiated with interferon-gamma (U937IFN). Caspase-3/-7 but not caspase-1 activation was observed in these infected cells and the exposure of PS occurred without the uptake of PI. An avirulent Shigella strain, wild-type Shigella killed with gentamicin, and even Escherichia coli strain JM109, could also induce apoptosis in U937IFN cells, and cytochalasin D could not prevent apoptosis. It appears therefore that Shigella-induced apoptosis of U937IFN cells is unrelated to Shigella pathogenicity and does not require bacterial internalization. Thus, Shigella can induce rapid necrosis of macrophage-like cells in a virulence-related manner by forming pores in the host cell membrane while some cells can be killed through apoptosis in a virulence-independent fashion.
Takashi Nonaka; Taku Kuwabara; Hitomi Mimuro; Asaomi Kuwae; Shinobu Imajoh-Ohmi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Microbiology (Reading, England)     Volume:  149     ISSN:  1350-0872     ISO Abbreviation:  Microbiology (Reading, Engl.)     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-09-01     Completed Date:  2004-03-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9430468     Medline TA:  Microbiology     Country:  England    
Other Details:
Languages:  eng     Pagination:  2513-27     Citation Subset:  IM    
Division of Cell Biology and Biochemistry, Department of Basic Medical Sciences, The Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
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MeSH Terms
Caspase 1 / metabolism
Cell Death
Cell Differentiation
Escherichia coli / drug effects,  physiology
Macrophages / microbiology*,  pathology
Shigella flexneri / pathogenicity,  physiology*
U937 Cells
Reg. No./Substance:
EC 1

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