Protease–antiprotease imbalances differ between Cystic Fibrosis patients' upper and lower airway secretions
Abstract Background Balanced levels of proteases and anti-proteases are essential in host defense systems. In CF patients' lungs, elevated protease/anti-protease-ratios contribute to damage of airway tissue and premature death with the inherited disease. Little is known about upper airway prote...
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| Veröffentlicht in: | Journal of cystic fibrosis 2015-05, Vol.14 (3), p.324-333 |
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| creator | Hentschel, Julia Fischer, Nele Janhsen, Wibke K Markert, Udo R Lehmann, Thomas Sonnemann, Jürgen Böer, Klas Pfister, Wolfgang Hipler, Uta-Christina Mainz, Jochen G |
| description | Abstract Background Balanced levels of proteases and anti-proteases are essential in host defense systems. In CF patients' lungs, elevated protease/anti-protease-ratios contribute to damage of airway tissue and premature death with the inherited disease. Little is known about upper airway protease equilibrium in CF. Methods Neutrophil elastase (NE), Secretory leukocyte protease inhibitor (SLPI), matrix metalloproteinase (MMP)9, tissue inhibitors of metalloproteinase (TIMP)1, cathepsin S (CTSS) and the corresponding cellular distribution were assessed in the nasal lavage (NL) and sputum of 40 CF patients. Results Concentrations of all proteases and anti-proteases were markedly higher in sputum than in NL (NE: 10-fold, SLPI: 5000-fold). Interestingly, the NE/SLPI ratio was 726-fold higher in NL compared to sputum, while the MMP9/TIMP1 ratio was 4.5-fold higher in sputum compared to NL. Discussion This first study to compare protease/anti-protease networks of CF upper and lower airways by NL and sputum reveals substantial differences between both compartments' immunological responses. This finding may have implications for sinonasal and pulmonary treatment, possibly leading to new therapeutic approaches. |
| doi_str_mv | 10.1016/j.jcf.2014.09.003 |
| format | Article |
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In CF patients' lungs, elevated protease/anti-protease-ratios contribute to damage of airway tissue and premature death with the inherited disease. Little is known about upper airway protease equilibrium in CF. Methods Neutrophil elastase (NE), Secretory leukocyte protease inhibitor (SLPI), matrix metalloproteinase (MMP)9, tissue inhibitors of metalloproteinase (TIMP)1, cathepsin S (CTSS) and the corresponding cellular distribution were assessed in the nasal lavage (NL) and sputum of 40 CF patients. Results Concentrations of all proteases and anti-proteases were markedly higher in sputum than in NL (NE: 10-fold, SLPI: 5000-fold). Interestingly, the NE/SLPI ratio was 726-fold higher in NL compared to sputum, while the MMP9/TIMP1 ratio was 4.5-fold higher in sputum compared to NL. Discussion This first study to compare protease/anti-protease networks of CF upper and lower airways by NL and sputum reveals substantial differences between both compartments' immunological responses. This finding may have implications for sinonasal and pulmonary treatment, possibly leading to new therapeutic approaches.</description><identifier>ISSN: 1569-1993</identifier><identifier>EISSN: 1873-5010</identifier><identifier>DOI: 10.1016/j.jcf.2014.09.003</identifier><identifier>PMID: 25286826</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Adolescent ; Adult ; Aged ; Cathepsin ; Child ; Child, Preschool ; Cystic Fibrosis - metabolism ; Cystic Fibrosis - pathology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Leukocyte Elastase - metabolism ; Lung ; Male ; Middle Aged ; Nasal lavage ; Nasal Lavage Fluid - chemistry ; Nasal Lavage Fluid - cytology ; Neutrophil elastase ; Protease ; Pulmonary/Respiratory ; Respiratory System - enzymology ; Respiratory System - pathology ; Secretory Leukocyte Peptidase Inhibitor - metabolism ; Sinonasal ; SLPI ; Sputum - cytology ; Sputum - enzymology ; Young Adult</subject><ispartof>Journal of cystic fibrosis, 2015-05, Vol.14 (3), p.324-333</ispartof><rights>European Cystic Fibrosis Society.</rights><rights>2014 European Cystic Fibrosis Society.</rights><rights>Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c521t-c89d91ff8e746ac7f9c4d27d89ecf78947ea718ec8393f9dbc29b82c11a81bd23</citedby><cites>FETCH-LOGICAL-c521t-c89d91ff8e746ac7f9c4d27d89ecf78947ea718ec8393f9dbc29b82c11a81bd23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1569199314002148$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25286826$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hentschel, Julia</creatorcontrib><creatorcontrib>Fischer, Nele</creatorcontrib><creatorcontrib>Janhsen, Wibke K</creatorcontrib><creatorcontrib>Markert, Udo R</creatorcontrib><creatorcontrib>Lehmann, Thomas</creatorcontrib><creatorcontrib>Sonnemann, Jürgen</creatorcontrib><creatorcontrib>Böer, Klas</creatorcontrib><creatorcontrib>Pfister, Wolfgang</creatorcontrib><creatorcontrib>Hipler, Uta-Christina</creatorcontrib><creatorcontrib>Mainz, Jochen G</creatorcontrib><title>Protease–antiprotease imbalances differ between Cystic Fibrosis patients' upper and lower airway secretions</title><title>Journal of cystic fibrosis</title><addtitle>J Cyst Fibros</addtitle><description>Abstract Background Balanced levels of proteases and anti-proteases are essential in host defense systems. In CF patients' lungs, elevated protease/anti-protease-ratios contribute to damage of airway tissue and premature death with the inherited disease. Little is known about upper airway protease equilibrium in CF. Methods Neutrophil elastase (NE), Secretory leukocyte protease inhibitor (SLPI), matrix metalloproteinase (MMP)9, tissue inhibitors of metalloproteinase (TIMP)1, cathepsin S (CTSS) and the corresponding cellular distribution were assessed in the nasal lavage (NL) and sputum of 40 CF patients. Results Concentrations of all proteases and anti-proteases were markedly higher in sputum than in NL (NE: 10-fold, SLPI: 5000-fold). Interestingly, the NE/SLPI ratio was 726-fold higher in NL compared to sputum, while the MMP9/TIMP1 ratio was 4.5-fold higher in sputum compared to NL. Discussion This first study to compare protease/anti-protease networks of CF upper and lower airways by NL and sputum reveals substantial differences between both compartments' immunological responses. This finding may have implications for sinonasal and pulmonary treatment, possibly leading to new therapeutic approaches.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Cathepsin</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Cystic Fibrosis - metabolism</subject><subject>Cystic Fibrosis - pathology</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Humans</subject><subject>Leukocyte Elastase - metabolism</subject><subject>Lung</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Nasal lavage</subject><subject>Nasal Lavage Fluid - chemistry</subject><subject>Nasal Lavage Fluid - cytology</subject><subject>Neutrophil elastase</subject><subject>Protease</subject><subject>Pulmonary/Respiratory</subject><subject>Respiratory System - enzymology</subject><subject>Respiratory System - pathology</subject><subject>Secretory Leukocyte Peptidase Inhibitor - metabolism</subject><subject>Sinonasal</subject><subject>SLPI</subject><subject>Sputum - cytology</subject><subject>Sputum - enzymology</subject><subject>Young Adult</subject><issn>1569-1993</issn><issn>1873-5010</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc2qFDEQhYMo3h99ADfSO910m0r3dBIE4TJ4VbigoK5DOqlA2v4zSd9hdr6Db-iTmGZGFy5cVRWcc-B8RcgzoBVQaF_1VW9cxSg0FZUVpfUDcgmC1-WOAn2Y910rS5CyviBXMfaUAqdcPCYXbMdEK1h7ScZPYU6oI_768VNPyS_ns_Bjpwc9GYyF9c5hKDpMB8Sp2B9j8qa49V2Yo4_FopPHKcUXxbosWacnWwzzYdt8OOhjEdEETH6e4hPyyOkh4tPzvCZfb99-2b8v7z6--7C_uSvNjkEqjZBWgnMCedNqw500jWXcConGcSEbjpqDQCNqWTtpO8NkJ5gB0AI6y-pr8vKUm-t8XzEmNfpocMiFcF6jgpZzIXjDNymcpCa3iQGdWoIfdTgqoGqjrHqVKauNsqJSZcrZ8_wcv3Yj2r-OP1iz4PVJgLnkvcegosmMDFof0CRlZ__f-Df_uM3gJ2_08A2PGPt5DVOmp0BFpqj6vL15-zI0lDJoRP0bAGSloQ</recordid><startdate>20150501</startdate><enddate>20150501</enddate><creator>Hentschel, Julia</creator><creator>Fischer, Nele</creator><creator>Janhsen, Wibke K</creator><creator>Markert, Udo R</creator><creator>Lehmann, Thomas</creator><creator>Sonnemann, Jürgen</creator><creator>Böer, Klas</creator><creator>Pfister, Wolfgang</creator><creator>Hipler, Uta-Christina</creator><creator>Mainz, Jochen G</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><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></search><sort><creationdate>20150501</creationdate><title>Protease–antiprotease imbalances differ between Cystic Fibrosis patients' upper and lower airway secretions</title><author>Hentschel, Julia ; Fischer, Nele ; Janhsen, Wibke K ; Markert, Udo R ; Lehmann, Thomas ; Sonnemann, Jürgen ; Böer, Klas ; Pfister, Wolfgang ; Hipler, Uta-Christina ; Mainz, Jochen G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c521t-c89d91ff8e746ac7f9c4d27d89ecf78947ea718ec8393f9dbc29b82c11a81bd23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Cathepsin</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Cystic Fibrosis - metabolism</topic><topic>Cystic Fibrosis - pathology</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Humans</topic><topic>Leukocyte Elastase - metabolism</topic><topic>Lung</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Nasal lavage</topic><topic>Nasal Lavage Fluid - chemistry</topic><topic>Nasal Lavage Fluid - cytology</topic><topic>Neutrophil elastase</topic><topic>Protease</topic><topic>Pulmonary/Respiratory</topic><topic>Respiratory System - enzymology</topic><topic>Respiratory System - pathology</topic><topic>Secretory Leukocyte Peptidase Inhibitor - metabolism</topic><topic>Sinonasal</topic><topic>SLPI</topic><topic>Sputum - cytology</topic><topic>Sputum - enzymology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hentschel, Julia</creatorcontrib><creatorcontrib>Fischer, Nele</creatorcontrib><creatorcontrib>Janhsen, Wibke K</creatorcontrib><creatorcontrib>Markert, Udo R</creatorcontrib><creatorcontrib>Lehmann, Thomas</creatorcontrib><creatorcontrib>Sonnemann, Jürgen</creatorcontrib><creatorcontrib>Böer, Klas</creatorcontrib><creatorcontrib>Pfister, Wolfgang</creatorcontrib><creatorcontrib>Hipler, Uta-Christina</creatorcontrib><creatorcontrib>Mainz, Jochen G</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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><jtitle>Journal of cystic fibrosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hentschel, Julia</au><au>Fischer, Nele</au><au>Janhsen, Wibke K</au><au>Markert, Udo R</au><au>Lehmann, Thomas</au><au>Sonnemann, Jürgen</au><au>Böer, Klas</au><au>Pfister, Wolfgang</au><au>Hipler, Uta-Christina</au><au>Mainz, Jochen G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protease–antiprotease imbalances differ between Cystic Fibrosis patients' upper and lower airway secretions</atitle><jtitle>Journal of cystic fibrosis</jtitle><addtitle>J Cyst Fibros</addtitle><date>2015-05-01</date><risdate>2015</risdate><volume>14</volume><issue>3</issue><spage>324</spage><epage>333</epage><pages>324-333</pages><issn>1569-1993</issn><eissn>1873-5010</eissn><abstract>Abstract Background Balanced levels of proteases and anti-proteases are essential in host defense systems. In CF patients' lungs, elevated protease/anti-protease-ratios contribute to damage of airway tissue and premature death with the inherited disease. Little is known about upper airway protease equilibrium in CF. Methods Neutrophil elastase (NE), Secretory leukocyte protease inhibitor (SLPI), matrix metalloproteinase (MMP)9, tissue inhibitors of metalloproteinase (TIMP)1, cathepsin S (CTSS) and the corresponding cellular distribution were assessed in the nasal lavage (NL) and sputum of 40 CF patients. Results Concentrations of all proteases and anti-proteases were markedly higher in sputum than in NL (NE: 10-fold, SLPI: 5000-fold). Interestingly, the NE/SLPI ratio was 726-fold higher in NL compared to sputum, while the MMP9/TIMP1 ratio was 4.5-fold higher in sputum compared to NL. Discussion This first study to compare protease/anti-protease networks of CF upper and lower airways by NL and sputum reveals substantial differences between both compartments' immunological responses. This finding may have implications for sinonasal and pulmonary treatment, possibly leading to new therapeutic approaches.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>25286826</pmid><doi>10.1016/j.jcf.2014.09.003</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aged Cathepsin Child Child, Preschool Cystic Fibrosis - metabolism Cystic Fibrosis - pathology Enzyme-Linked Immunosorbent Assay Female Humans Leukocyte Elastase - metabolism Lung Male Middle Aged Nasal lavage Nasal Lavage Fluid - chemistry Nasal Lavage Fluid - cytology Neutrophil elastase Protease Pulmonary/Respiratory Respiratory System - enzymology Respiratory System - pathology Secretory Leukocyte Peptidase Inhibitor - metabolism Sinonasal SLPI Sputum - cytology Sputum - enzymology Young Adult |
| title | Protease–antiprotease imbalances differ between Cystic Fibrosis patients' upper and lower airway secretions |
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