Statins enhance formation of phagocyte extracellular traps
Statins are inhibitors of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis. Recent clinico-epidemiologic studies correlate patients receiving statin therapy with having reduced mortality associated with severe bacterial infection. Invest...
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| Veröffentlicht in: | Cell host & microbe 2010-11, Vol.8 (5), p.445-454 |
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| creator | Chow, Ohn A von Köckritz-Blickwede, Maren Bright, A Taylor Hensler, Mary E Zinkernagel, Annelies S Cogen, Anna L Gallo, Richard L Monestier, Marc Wang, Yanming Glass, Christopher K Nizet, Victor |
| description | Statins are inhibitors of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis. Recent clinico-epidemiologic studies correlate patients receiving statin therapy with having reduced mortality associated with severe bacterial infection. Investigating the effect of statins on the innate immune capacity of phagocytic cells against the human pathogen Staphylococcus aureus, we uncovered a beneficial effect of statins on bacterial clearance by phagocytes, although, paradoxically, both phagocytosis and oxidative burst were inhibited. Probing instead for an extracellular mechanism of killing, we found that statins boosted the production of antibacterial DNA-based extracellular traps (ETs) by human and murine neutrophils and also monocytes/macrophages. The effect of statins to induce phagocyte ETs was linked to sterol pathway inhibition. We conclude that a drug therapy taken chronically by millions alters the functional behavior of phagocytic cells, which could have ramifications for susceptibility and response to bacterial infections in these patients. |
| doi_str_mv | 10.1016/j.chom.2010.10.005 |
| format | Article |
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Recent clinico-epidemiologic studies correlate patients receiving statin therapy with having reduced mortality associated with severe bacterial infection. Investigating the effect of statins on the innate immune capacity of phagocytic cells against the human pathogen Staphylococcus aureus, we uncovered a beneficial effect of statins on bacterial clearance by phagocytes, although, paradoxically, both phagocytosis and oxidative burst were inhibited. Probing instead for an extracellular mechanism of killing, we found that statins boosted the production of antibacterial DNA-based extracellular traps (ETs) by human and murine neutrophils and also monocytes/macrophages. The effect of statins to induce phagocyte ETs was linked to sterol pathway inhibition. We conclude that a drug therapy taken chronically by millions alters the functional behavior of phagocytic cells, which could have ramifications for susceptibility and response to bacterial infections in these patients.</description><identifier>ISSN: 1931-3128</identifier><identifier>EISSN: 1934-6069</identifier><identifier>DOI: 10.1016/j.chom.2010.10.005</identifier><identifier>PMID: 21075355</identifier><language>eng</language><publisher>United States</publisher><subject>Acyl Coenzyme A - antagonists & inhibitors ; Animals ; Cells, Cultured ; DNA, Bacterial - drug effects ; DNA, Bacterial - immunology ; Extracellular Space - immunology ; Extracellular Space - metabolism ; Extracellular Space - microbiology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use ; Macrophages - drug effects ; Macrophages - immunology ; Macrophages - microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CFTR ; Neutrophils - drug effects ; Neutrophils - immunology ; Neutrophils - microbiology ; Phagocytes - drug effects ; Phagocytes - immunology ; Phagocytes - microbiology ; Pneumonia, Staphylococcal - drug therapy ; Pneumonia, Staphylococcal - immunology ; Pneumonia, Staphylococcal - microbiology ; Staphylococcus aureus - drug effects</subject><ispartof>Cell host & microbe, 2010-11, Vol.8 (5), p.445-454</ispartof><rights>Copyright © 2010 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c467t-4561eb179d893e852f2ec2abc70184b7c1311f7d9fe0f67cf664f77c93933fbf3</citedby><cites>FETCH-LOGICAL-c467t-4561eb179d893e852f2ec2abc70184b7c1311f7d9fe0f67cf664f77c93933fbf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21075355$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chow, Ohn A</creatorcontrib><creatorcontrib>von Köckritz-Blickwede, Maren</creatorcontrib><creatorcontrib>Bright, A Taylor</creatorcontrib><creatorcontrib>Hensler, Mary E</creatorcontrib><creatorcontrib>Zinkernagel, Annelies S</creatorcontrib><creatorcontrib>Cogen, Anna L</creatorcontrib><creatorcontrib>Gallo, Richard L</creatorcontrib><creatorcontrib>Monestier, Marc</creatorcontrib><creatorcontrib>Wang, Yanming</creatorcontrib><creatorcontrib>Glass, Christopher K</creatorcontrib><creatorcontrib>Nizet, Victor</creatorcontrib><title>Statins enhance formation of phagocyte extracellular traps</title><title>Cell host & microbe</title><addtitle>Cell Host Microbe</addtitle><description>Statins are inhibitors of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis. Recent clinico-epidemiologic studies correlate patients receiving statin therapy with having reduced mortality associated with severe bacterial infection. Investigating the effect of statins on the innate immune capacity of phagocytic cells against the human pathogen Staphylococcus aureus, we uncovered a beneficial effect of statins on bacterial clearance by phagocytes, although, paradoxically, both phagocytosis and oxidative burst were inhibited. Probing instead for an extracellular mechanism of killing, we found that statins boosted the production of antibacterial DNA-based extracellular traps (ETs) by human and murine neutrophils and also monocytes/macrophages. The effect of statins to induce phagocyte ETs was linked to sterol pathway inhibition. We conclude that a drug therapy taken chronically by millions alters the functional behavior of phagocytic cells, which could have ramifications for susceptibility and response to bacterial infections in these patients.</description><subject>Acyl Coenzyme A - antagonists & inhibitors</subject><subject>Animals</subject><subject>Cells, Cultured</subject><subject>DNA, Bacterial - drug effects</subject><subject>DNA, Bacterial - immunology</subject><subject>Extracellular Space - immunology</subject><subject>Extracellular Space - metabolism</subject><subject>Extracellular Space - microbiology</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - immunology</subject><subject>Macrophages - microbiology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Inbred CFTR</subject><subject>Neutrophils - drug effects</subject><subject>Neutrophils - immunology</subject><subject>Neutrophils - microbiology</subject><subject>Phagocytes - drug effects</subject><subject>Phagocytes - immunology</subject><subject>Phagocytes - microbiology</subject><subject>Pneumonia, Staphylococcal - drug therapy</subject><subject>Pneumonia, Staphylococcal - immunology</subject><subject>Pneumonia, Staphylococcal - microbiology</subject><subject>Staphylococcus aureus - drug effects</subject><issn>1931-3128</issn><issn>1934-6069</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkM1OwzAQhC0EoqXwAhxQbpwSvHFsJxyQUMWfVIkDcLYc125SJXGwE0TfnqQtFZx2NZ6d9X4IXQKOAAO7WUeqsHUU460QYUyP0BQykoQMs-x420NIIE4n6Mz79WCgmMMpmsSAOSWUTtHtWye7svGBbgrZKB0Y6-pBsU1gTdAWcmXVptOB_u6cVLqq-kq6YOhbf45OjKy8vtjXGfp4fHifP4eL16eX-f0iVAnjXZhQBjoHni3TjOiUxibWKpa54hjSJOcKCIDhy8xobBhXhrHEcK4ykhFickNm6G6X2_Z5rZdKN8P6SrSurKXbCCtL8f-lKQuxsl-CYJwmgIeA632As5-99p2oSz_eIhttey94ynFCgYzOeOdUznrvtDlsASxG5mItRuZiZD5qA9Jh6Orv_w4jv5DJD5bCf84</recordid><startdate>20101118</startdate><enddate>20101118</enddate><creator>Chow, Ohn A</creator><creator>von Köckritz-Blickwede, Maren</creator><creator>Bright, A Taylor</creator><creator>Hensler, Mary E</creator><creator>Zinkernagel, Annelies S</creator><creator>Cogen, Anna L</creator><creator>Gallo, Richard L</creator><creator>Monestier, Marc</creator><creator>Wang, Yanming</creator><creator>Glass, Christopher K</creator><creator>Nizet, Victor</creator><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20101118</creationdate><title>Statins enhance formation of phagocyte extracellular traps</title><author>Chow, Ohn A ; von Köckritz-Blickwede, Maren ; Bright, A Taylor ; Hensler, Mary E ; Zinkernagel, Annelies S ; Cogen, Anna L ; Gallo, Richard L ; Monestier, Marc ; Wang, Yanming ; Glass, Christopher K ; Nizet, Victor</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-4561eb179d893e852f2ec2abc70184b7c1311f7d9fe0f67cf664f77c93933fbf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acyl Coenzyme A - antagonists & inhibitors</topic><topic>Animals</topic><topic>Cells, Cultured</topic><topic>DNA, Bacterial - drug effects</topic><topic>DNA, Bacterial - immunology</topic><topic>Extracellular Space - immunology</topic><topic>Extracellular Space - metabolism</topic><topic>Extracellular Space - microbiology</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - immunology</topic><topic>Macrophages - microbiology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Inbred CFTR</topic><topic>Neutrophils - drug effects</topic><topic>Neutrophils - immunology</topic><topic>Neutrophils - microbiology</topic><topic>Phagocytes - drug effects</topic><topic>Phagocytes - immunology</topic><topic>Phagocytes - microbiology</topic><topic>Pneumonia, Staphylococcal - drug therapy</topic><topic>Pneumonia, Staphylococcal - immunology</topic><topic>Pneumonia, Staphylococcal - microbiology</topic><topic>Staphylococcus aureus - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chow, Ohn A</creatorcontrib><creatorcontrib>von Köckritz-Blickwede, Maren</creatorcontrib><creatorcontrib>Bright, A Taylor</creatorcontrib><creatorcontrib>Hensler, Mary E</creatorcontrib><creatorcontrib>Zinkernagel, Annelies S</creatorcontrib><creatorcontrib>Cogen, Anna L</creatorcontrib><creatorcontrib>Gallo, Richard L</creatorcontrib><creatorcontrib>Monestier, Marc</creatorcontrib><creatorcontrib>Wang, Yanming</creatorcontrib><creatorcontrib>Glass, Christopher K</creatorcontrib><creatorcontrib>Nizet, Victor</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell host & microbe</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chow, Ohn A</au><au>von Köckritz-Blickwede, Maren</au><au>Bright, A Taylor</au><au>Hensler, Mary E</au><au>Zinkernagel, Annelies S</au><au>Cogen, Anna L</au><au>Gallo, Richard L</au><au>Monestier, Marc</au><au>Wang, Yanming</au><au>Glass, Christopher K</au><au>Nizet, Victor</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Statins enhance formation of phagocyte extracellular traps</atitle><jtitle>Cell host & microbe</jtitle><addtitle>Cell Host Microbe</addtitle><date>2010-11-18</date><risdate>2010</risdate><volume>8</volume><issue>5</issue><spage>445</spage><epage>454</epage><pages>445-454</pages><issn>1931-3128</issn><eissn>1934-6069</eissn><abstract>Statins are inhibitors of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis. 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| ispartof | Cell host & microbe, 2010-11, Vol.8 (5), p.445-454 |
| issn | 1931-3128 1934-6069 |
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| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; EZB-FREE-00999 freely available EZB journals |
| subjects | Acyl Coenzyme A - antagonists & inhibitors Animals Cells, Cultured DNA, Bacterial - drug effects DNA, Bacterial - immunology Extracellular Space - immunology Extracellular Space - metabolism Extracellular Space - microbiology Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use Macrophages - drug effects Macrophages - immunology Macrophages - microbiology Male Mice Mice, Inbred C57BL Mice, Inbred CFTR Neutrophils - drug effects Neutrophils - immunology Neutrophils - microbiology Phagocytes - drug effects Phagocytes - immunology Phagocytes - microbiology Pneumonia, Staphylococcal - drug therapy Pneumonia, Staphylococcal - immunology Pneumonia, Staphylococcal - microbiology Staphylococcus aureus - drug effects |
| title | Statins enhance formation of phagocyte extracellular traps |
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