The Osmolyte Xylitol Reduces the Salt Concentration of Airway Surface Liquid and May Enhance Bacterial Killing
The thin layer of airway surface liquid (ASL) contains antimicrobial substances that kill the small numbers of bacteria that are constantly being deposited in the lungs. An increase in ASL salt concentration inhibits the activity of airway antimicrobial factors and may partially explain the pathogen...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2000-10, Vol.97 (21), p.11614-11619 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Zabner, Joseph Seiler, Michael P. Launspach, Janice L. Karp, Philip H. Kearney, William R. Look, Dwight C. Smith, Jeffrey J. Welsh, Michael J. |
| description | The thin layer of airway surface liquid (ASL) contains antimicrobial substances that kill the small numbers of bacteria that are constantly being deposited in the lungs. An increase in ASL salt concentration inhibits the activity of airway antimicrobial factors and may partially explain the pathogenesis of cystic fibrosis (CF). We tested the hypothesis that an osmolyte with a low transepithelial permeability may lower the ASL salt concentration, thereby enhancing innate immunity. We found that the five-carbon sugar xylitol has a low transepithelial permeability, is poorly metabolized by several bacteria, and can lower the ASL salt concentration in both CF and non-CF airway epithelia in vitro. Furthermore, in a double-blind, randomized, crossover study, xylitol sprayed for 4 days into each nostril of normal volunteers significantly decreased the number of nasal coagulase-negative Staphylococcus compared with saline control. Xylitol may be of value in decreasing ASL salt concentration and enhancing the innate antimicrobial defense at the airway surface. |
| doi_str_mv | 10.1073/pnas.97.21.11614 |
| format | Article |
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An increase in ASL salt concentration inhibits the activity of airway antimicrobial factors and may partially explain the pathogenesis of cystic fibrosis (CF). We tested the hypothesis that an osmolyte with a low transepithelial permeability may lower the ASL salt concentration, thereby enhancing innate immunity. We found that the five-carbon sugar xylitol has a low transepithelial permeability, is poorly metabolized by several bacteria, and can lower the ASL salt concentration in both CF and non-CF airway epithelia in vitro. Furthermore, in a double-blind, randomized, crossover study, xylitol sprayed for 4 days into each nostril of normal volunteers significantly decreased the number of nasal coagulase-negative Staphylococcus compared with saline control. Xylitol may be of value in decreasing ASL salt concentration and enhancing the innate antimicrobial defense at the airway surface.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.97.21.11614</identifier><identifier>PMID: 11027360</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Adult ; airway surface liquid ; Antibacterials ; Antibiotics ; Antimicrobials ; Bacteria ; Bacteria - drug effects ; Biological Sciences ; Bronchi - chemistry ; Bronchi - drug effects ; Bronchi - microbiology ; Cell Membrane Permeability - drug effects ; Chlorides - metabolism ; Colony Count, Microbial ; Cystic fibrosis ; Cystic Fibrosis - metabolism ; Cystic Fibrosis - microbiology ; Epithelial Cells - chemistry ; Epithelial Cells - drug effects ; Epithelial Cells - microbiology ; Epithelium ; Female ; Humans ; Infections ; Liquids ; Lungs ; Male ; Medical research ; Middle Aged ; Nasal Mucosa - drug effects ; Nasal Mucosa - microbiology ; Osmolar Concentration ; Salinity effects ; Salt ; Salts - chemistry ; Staphylococcus ; Trachea - chemistry ; Trachea - drug effects ; Trachea - microbiology ; xylitol ; Xylitol - chemistry ; Xylitol - pharmacology</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2000-10, Vol.97 (21), p.11614-11619</ispartof><rights>Copyright 1993-2000 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Oct 10, 2000</rights><rights>Copyright © 2000, The National Academy of Sciences 2000</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c591t-2539f29b7d7cad71b091f1f096c6dd648618e3f90b85ce452c8f44ee990661b63</citedby><cites>FETCH-LOGICAL-c591t-2539f29b7d7cad71b091f1f096c6dd648618e3f90b85ce452c8f44ee990661b63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/97/21.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/123445$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/123445$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27903,27904,53769,53771,57995,58228</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11027360$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zabner, Joseph</creatorcontrib><creatorcontrib>Seiler, Michael P.</creatorcontrib><creatorcontrib>Launspach, Janice L.</creatorcontrib><creatorcontrib>Karp, Philip H.</creatorcontrib><creatorcontrib>Kearney, William R.</creatorcontrib><creatorcontrib>Look, Dwight C.</creatorcontrib><creatorcontrib>Smith, Jeffrey J.</creatorcontrib><creatorcontrib>Welsh, Michael J.</creatorcontrib><title>The Osmolyte Xylitol Reduces the Salt Concentration of Airway Surface Liquid and May Enhance Bacterial Killing</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>The thin layer of airway surface liquid (ASL) contains antimicrobial substances that kill the small numbers of bacteria that are constantly being deposited in the lungs. An increase in ASL salt concentration inhibits the activity of airway antimicrobial factors and may partially explain the pathogenesis of cystic fibrosis (CF). We tested the hypothesis that an osmolyte with a low transepithelial permeability may lower the ASL salt concentration, thereby enhancing innate immunity. We found that the five-carbon sugar xylitol has a low transepithelial permeability, is poorly metabolized by several bacteria, and can lower the ASL salt concentration in both CF and non-CF airway epithelia in vitro. Furthermore, in a double-blind, randomized, crossover study, xylitol sprayed for 4 days into each nostril of normal volunteers significantly decreased the number of nasal coagulase-negative Staphylococcus compared with saline control. Xylitol may be of value in decreasing ASL salt concentration and enhancing the innate antimicrobial defense at the airway surface.</description><subject>Adult</subject><subject>airway surface liquid</subject><subject>Antibacterials</subject><subject>Antibiotics</subject><subject>Antimicrobials</subject><subject>Bacteria</subject><subject>Bacteria - drug effects</subject><subject>Biological Sciences</subject><subject>Bronchi - chemistry</subject><subject>Bronchi - drug effects</subject><subject>Bronchi - microbiology</subject><subject>Cell Membrane Permeability - drug effects</subject><subject>Chlorides - metabolism</subject><subject>Colony Count, Microbial</subject><subject>Cystic fibrosis</subject><subject>Cystic Fibrosis - metabolism</subject><subject>Cystic Fibrosis - microbiology</subject><subject>Epithelial Cells - chemistry</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - microbiology</subject><subject>Epithelium</subject><subject>Female</subject><subject>Humans</subject><subject>Infections</subject><subject>Liquids</subject><subject>Lungs</subject><subject>Male</subject><subject>Medical research</subject><subject>Middle Aged</subject><subject>Nasal Mucosa - drug effects</subject><subject>Nasal Mucosa - microbiology</subject><subject>Osmolar Concentration</subject><subject>Salinity effects</subject><subject>Salt</subject><subject>Salts - chemistry</subject><subject>Staphylococcus</subject><subject>Trachea - chemistry</subject><subject>Trachea - drug effects</subject><subject>Trachea - microbiology</subject><subject>xylitol</subject><subject>Xylitol - chemistry</subject><subject>Xylitol - pharmacology</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1v0zAYxiMEYmVwR0ICiwPikuLXcexY2mVU40MUTWJD4mY5jrO6cu3OdoD-9yS0MMYBTpb8_J736ymKx4DngHn1autVmgs-JzAHYEDvFDPAAkpGBb5bzDAmvGwooUfFg5TWGGNRN_h-cQQwKhXDs8Jfrgw6T5vgdtmgLztnc3Dok-kGbRLKo3ihXEaL4LXxOapsg0ehR6c2flM7dDHEXmmDlvZ6sB1SvkMfx-8zv1KjAb1WOptolUMfrHPWXz0s7vXKJfPo8B4Xn9-cXS7elcvzt-8Xp8tS1wJySepK9ES0vONadRzacakeeiyYZl3HaMOgMVUvcNvU2tCa6Kan1BghMGPQsuq4ONnX3Q7txnT72Z3cRrtRcSeDsvK24u1KXoWvEjihYrS_ONhjuB5MynJjkzbOKW_CkCQnFTQMk_-CwDlQQaeBnv8FrsMQ_XgDSTBUFQg-tcV7SMeQUjT974EByylwOQUuBZcE5M_AR8vTPxe9MRwSHoFnB2Cy_pJvl3j5b0L2g3PZfM8j-mSPrlMO8aYZqSitqx-l-ckq</recordid><startdate>20001010</startdate><enddate>20001010</enddate><creator>Zabner, Joseph</creator><creator>Seiler, Michael P.</creator><creator>Launspach, Janice L.</creator><creator>Karp, Philip H.</creator><creator>Kearney, William R.</creator><creator>Look, Dwight C.</creator><creator>Smith, Jeffrey J.</creator><creator>Welsh, Michael J.</creator><general>National Academy of Sciences of the United States of America</general><general>National Acad Sciences</general><general>National Academy of Sciences</general><general>The National Academy of Sciences</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20001010</creationdate><title>The Osmolyte Xylitol Reduces the Salt Concentration of Airway Surface Liquid and May Enhance Bacterial Killing</title><author>Zabner, Joseph ; 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An increase in ASL salt concentration inhibits the activity of airway antimicrobial factors and may partially explain the pathogenesis of cystic fibrosis (CF). We tested the hypothesis that an osmolyte with a low transepithelial permeability may lower the ASL salt concentration, thereby enhancing innate immunity. We found that the five-carbon sugar xylitol has a low transepithelial permeability, is poorly metabolized by several bacteria, and can lower the ASL salt concentration in both CF and non-CF airway epithelia in vitro. Furthermore, in a double-blind, randomized, crossover study, xylitol sprayed for 4 days into each nostril of normal volunteers significantly decreased the number of nasal coagulase-negative Staphylococcus compared with saline control. Xylitol may be of value in decreasing ASL salt concentration and enhancing the innate antimicrobial defense at the airway surface.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>11027360</pmid><doi>10.1073/pnas.97.21.11614</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult airway surface liquid Antibacterials Antibiotics Antimicrobials Bacteria Bacteria - drug effects Biological Sciences Bronchi - chemistry Bronchi - drug effects Bronchi - microbiology Cell Membrane Permeability - drug effects Chlorides - metabolism Colony Count, Microbial Cystic fibrosis Cystic Fibrosis - metabolism Cystic Fibrosis - microbiology Epithelial Cells - chemistry Epithelial Cells - drug effects Epithelial Cells - microbiology Epithelium Female Humans Infections Liquids Lungs Male Medical research Middle Aged Nasal Mucosa - drug effects Nasal Mucosa - microbiology Osmolar Concentration Salinity effects Salt Salts - chemistry Staphylococcus Trachea - chemistry Trachea - drug effects Trachea - microbiology xylitol Xylitol - chemistry Xylitol - pharmacology |
| title | The Osmolyte Xylitol Reduces the Salt Concentration of Airway Surface Liquid and May Enhance Bacterial Killing |
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