Lethal toxin of Bacillus anthracis causes apoptosis of macrophages
Lethal toxin is a major anthrax virulence factor, causing the rapid death of experimental animals. Lethal toxin can enter most cell types, but only certain macrophages and cell lines are susceptible to toxin-mediated cytolysis. We have shown that in murine RAW 264.7 cells, sublytic amounts of lethal...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2002-04, Vol.293 (1), p.349-355 |
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| creator | Popov, Serguei G Villasmil, Rafael Bernardi, Jessica Grene, Edith Cardwell, Jennifer Wu, Aiguo Alibek, Darya Bailey, Charles Alibek, Ken |
| description | Lethal toxin is a major anthrax virulence factor, causing the rapid death of experimental animals. Lethal toxin can enter most cell types, but only certain macrophages and cell lines are susceptible to toxin-mediated cytolysis. We have shown that in murine RAW 264.7 cells, sublytic amounts of lethal toxin trigger intracellular signaling events typical for apoptosis, including changes in membrane permeability, loss of mitochondrial membrane potential, and DNA fragmentation. The cells were protected from the toxin by specific inhibitors of caspase-1, -2, -3, -4, -6, and -8. Phagocytic activity of macrophages was inhibited by sublytic concentrations of lethal toxin. Infection of cells with anthrax (Sterne) spores impaired their bactericidal capacity, which could be reversed by a lethal toxin inhibitor, bestatin. We suggest that apoptosis rather than direct lysis is biologically relevant to lethal toxin intracellular activity. |
| doi_str_mv | 10.1016/S0006-291X(02)00227-9 |
| format | Article |
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Lethal toxin can enter most cell types, but only certain macrophages and cell lines are susceptible to toxin-mediated cytolysis. We have shown that in murine RAW 264.7 cells, sublytic amounts of lethal toxin trigger intracellular signaling events typical for apoptosis, including changes in membrane permeability, loss of mitochondrial membrane potential, and DNA fragmentation. The cells were protected from the toxin by specific inhibitors of caspase-1, -2, -3, -4, -6, and -8. Phagocytic activity of macrophages was inhibited by sublytic concentrations of lethal toxin. Infection of cells with anthrax (Sterne) spores impaired their bactericidal capacity, which could be reversed by a lethal toxin inhibitor, bestatin. We suggest that apoptosis rather than direct lysis is biologically relevant to lethal toxin intracellular activity.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/S0006-291X(02)00227-9</identifier><identifier>PMID: 12054607</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Anthrax ; Antigens, Bacterial ; Apoptosis ; Apoptosis - drug effects ; Bacillus anthracis ; Bacterial Toxins ; Bactericidal activity ; Carrier Proteins - antagonists & inhibitors ; Carrier Proteins - toxicity ; Caspase 3 ; Caspase 8 ; Caspase 9 ; Caspase Inhibitors ; Cell Line ; Cysteine Proteinase Inhibitors - pharmacology ; Lethal toxin ; Macrophages ; Macrophages - cytology ; Macrophages - drug effects ; Macrophages - physiology ; Mice</subject><ispartof>Biochemical and biophysical research communications, 2002-04, Vol.293 (1), p.349-355</ispartof><rights>2002 Elsevier Science (USA)</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c392t-8b611c5658e02f4c631d51e0de37446783347d766b0bf46a3e22adb27d62aa833</citedby><cites>FETCH-LOGICAL-c392t-8b611c5658e02f4c631d51e0de37446783347d766b0bf46a3e22adb27d62aa833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0006291X02002279$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12054607$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Popov, Serguei G</creatorcontrib><creatorcontrib>Villasmil, Rafael</creatorcontrib><creatorcontrib>Bernardi, Jessica</creatorcontrib><creatorcontrib>Grene, Edith</creatorcontrib><creatorcontrib>Cardwell, Jennifer</creatorcontrib><creatorcontrib>Wu, Aiguo</creatorcontrib><creatorcontrib>Alibek, Darya</creatorcontrib><creatorcontrib>Bailey, Charles</creatorcontrib><creatorcontrib>Alibek, Ken</creatorcontrib><title>Lethal toxin of Bacillus anthracis causes apoptosis of macrophages</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>Lethal toxin is a major anthrax virulence factor, causing the rapid death of experimental animals. Lethal toxin can enter most cell types, but only certain macrophages and cell lines are susceptible to toxin-mediated cytolysis. We have shown that in murine RAW 264.7 cells, sublytic amounts of lethal toxin trigger intracellular signaling events typical for apoptosis, including changes in membrane permeability, loss of mitochondrial membrane potential, and DNA fragmentation. The cells were protected from the toxin by specific inhibitors of caspase-1, -2, -3, -4, -6, and -8. Phagocytic activity of macrophages was inhibited by sublytic concentrations of lethal toxin. Infection of cells with anthrax (Sterne) spores impaired their bactericidal capacity, which could be reversed by a lethal toxin inhibitor, bestatin. We suggest that apoptosis rather than direct lysis is biologically relevant to lethal toxin intracellular activity.</description><subject>Animals</subject><subject>Anthrax</subject><subject>Antigens, Bacterial</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Bacillus anthracis</subject><subject>Bacterial Toxins</subject><subject>Bactericidal activity</subject><subject>Carrier Proteins - antagonists & inhibitors</subject><subject>Carrier Proteins - toxicity</subject><subject>Caspase 3</subject><subject>Caspase 8</subject><subject>Caspase 9</subject><subject>Caspase Inhibitors</subject><subject>Cell Line</subject><subject>Cysteine Proteinase Inhibitors - pharmacology</subject><subject>Lethal toxin</subject><subject>Macrophages</subject><subject>Macrophages - cytology</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - physiology</subject><subject>Mice</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1LxDAQhoMo7rr6E5SeRA_VSZom25O4i1-w4EEFbyFNpm6kXzat6L83-4EePYXMPJN38hByTOGCAhWXTwAgYpbR1zNg5wCMyTjbIWMKGcSMAt8l419kRA68fweglItsn4wog5QLkGMyW2C_1GXUN1-ujpoimmnjynLwka77ZRcuPjJ68BgKbdP2jQ-FgFXadE271G_oD8leoUuPR9tzQl5ub57n9_Hi8e5hfr2ITZKxPp7mglKTinSKwApuREJtShEsJpJzIadJwqWVQuSQF1zoBBnTNmfSCqZ16E7I6ebdtms-BvS9qpw3WJa6xmbwimZSyDThAUw3YFjR-w4L1Xau0t23oqBW8tRanlqZUcDUWp7KwtzJNmDIK7R_U1tbAbjaABi--emwU944rA1a16HplW3cPxE_F-x-GQ</recordid><startdate>20020426</startdate><enddate>20020426</enddate><creator>Popov, Serguei G</creator><creator>Villasmil, Rafael</creator><creator>Bernardi, Jessica</creator><creator>Grene, Edith</creator><creator>Cardwell, Jennifer</creator><creator>Wu, Aiguo</creator><creator>Alibek, Darya</creator><creator>Bailey, Charles</creator><creator>Alibek, Ken</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T5</scope><scope>7U7</scope><scope>C1K</scope><scope>H94</scope></search><sort><creationdate>20020426</creationdate><title>Lethal toxin of Bacillus anthracis causes apoptosis of macrophages</title><author>Popov, Serguei G ; Villasmil, Rafael ; Bernardi, Jessica ; Grene, Edith ; Cardwell, Jennifer ; Wu, Aiguo ; Alibek, Darya ; Bailey, Charles ; Alibek, Ken</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c392t-8b611c5658e02f4c631d51e0de37446783347d766b0bf46a3e22adb27d62aa833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Anthrax</topic><topic>Antigens, Bacterial</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Bacillus anthracis</topic><topic>Bacterial Toxins</topic><topic>Bactericidal activity</topic><topic>Carrier Proteins - antagonists & inhibitors</topic><topic>Carrier Proteins - toxicity</topic><topic>Caspase 3</topic><topic>Caspase 8</topic><topic>Caspase 9</topic><topic>Caspase Inhibitors</topic><topic>Cell Line</topic><topic>Cysteine Proteinase Inhibitors - pharmacology</topic><topic>Lethal toxin</topic><topic>Macrophages</topic><topic>Macrophages - cytology</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - physiology</topic><topic>Mice</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Popov, Serguei G</creatorcontrib><creatorcontrib>Villasmil, Rafael</creatorcontrib><creatorcontrib>Bernardi, Jessica</creatorcontrib><creatorcontrib>Grene, Edith</creatorcontrib><creatorcontrib>Cardwell, Jennifer</creatorcontrib><creatorcontrib>Wu, Aiguo</creatorcontrib><creatorcontrib>Alibek, Darya</creatorcontrib><creatorcontrib>Bailey, Charles</creatorcontrib><creatorcontrib>Alibek, Ken</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Immunology Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Popov, Serguei G</au><au>Villasmil, Rafael</au><au>Bernardi, Jessica</au><au>Grene, Edith</au><au>Cardwell, Jennifer</au><au>Wu, Aiguo</au><au>Alibek, Darya</au><au>Bailey, Charles</au><au>Alibek, Ken</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lethal toxin of Bacillus anthracis causes apoptosis of macrophages</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2002-04-26</date><risdate>2002</risdate><volume>293</volume><issue>1</issue><spage>349</spage><epage>355</epage><pages>349-355</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Lethal toxin is a major anthrax virulence factor, causing the rapid death of experimental animals. 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| subjects | Animals Anthrax Antigens, Bacterial Apoptosis Apoptosis - drug effects Bacillus anthracis Bacterial Toxins Bactericidal activity Carrier Proteins - antagonists & inhibitors Carrier Proteins - toxicity Caspase 3 Caspase 8 Caspase 9 Caspase Inhibitors Cell Line Cysteine Proteinase Inhibitors - pharmacology Lethal toxin Macrophages Macrophages - cytology Macrophages - drug effects Macrophages - physiology Mice |
| title | Lethal toxin of Bacillus anthracis causes apoptosis of macrophages |
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