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Reaction products of hexamethylene diisocyanate vapors with "self" molecules in the airways of rabbits exposed via tracheostomy
1. Hexamethylenediisocyanate (HDI) is a widely used aliphatic diisocyanate and a well-recognized cause of occupational asthma. 2. "Self" molecules (peptides/proteins) in the lower airways, susceptible to chemical reactivity with HDI, have been hypothesized to play a role in asthma pathogen...
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| Published in: | Xenobiotica 2018-05, Vol.48 (5), p.488-497 |
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| Main Authors: | , , , , , , , , |
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| cites | cdi_FETCH-LOGICAL-c468t-e46a79f0d6e94f71d6dee971c544e08cc38e6084f2e4bfe65a058da37fe791a03 |
| container_end_page | 497 |
| container_issue | 5 |
| container_start_page | 488 |
| container_title | Xenobiotica |
| container_volume | 48 |
| creator | Wisnewski, Adam V. Kanyo, Jean Asher, Jennifer Goodrich, James A. Barnett, Grace Patrylak, Lyn Liu, Jian Redlich, Carrie A. Nassar, Ala F. |
| description | 1. Hexamethylenediisocyanate (HDI) is a widely used aliphatic diisocyanate and a well-recognized cause of occupational asthma.
2. "Self" molecules (peptides/proteins) in the lower airways, susceptible to chemical reactivity with HDI, have been hypothesized to play a role in asthma pathogenesis and/or chemical metabolism, but remain poorly characterized.
3. This study employed unique approaches to identify and characterize "self" targets of HDI reactivity in the lower airways. Anesthetized rabbits free breathed through a tracheostomy tube connected to chambers containing either, O
2
, or O
2
plus ∼200 ppb HDI vapors. Following 60 minutes of exposure, the airways were lavaged and the fluid was analyzed by LC-MS and LC-MS/MS.
4. The low-molecular weight (3 kDa) fraction of exposed rabbit BAL fluid identified HDI modification of specific lysines in uteroglobin (aka clara cell protein) and albumin.
5. In summary, this study utilized a unique approach to chemical vapor exposure in rabbits, to identify HDI reaction products with "self" molecules in the lower airways. |
| doi_str_mv | 10.1080/00498254.2017.1329569 |
| format | article |
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2. "Self" molecules (peptides/proteins) in the lower airways, susceptible to chemical reactivity with HDI, have been hypothesized to play a role in asthma pathogenesis and/or chemical metabolism, but remain poorly characterized.
3. This study employed unique approaches to identify and characterize "self" targets of HDI reactivity in the lower airways. Anesthetized rabbits free breathed through a tracheostomy tube connected to chambers containing either, O
2
, or O
2
plus ∼200 ppb HDI vapors. Following 60 minutes of exposure, the airways were lavaged and the fluid was analyzed by LC-MS and LC-MS/MS.
4. The low-molecular weight (<3 kDa) fraction of HDI exposed, but not control rabbit bronchoalveolar lavage (BAL) fluid identified 783.26 and 476.18 m/z [M+H]
+
ions with high energy collision-induced dissociation (HCD) fragmentation patterns consistent with bis glutathione (GSH)-HDI and mono(GSH)-HDI. Proteomic analyses of the high molecular weight (>3 kDa) fraction of exposed rabbit BAL fluid identified HDI modification of specific lysines in uteroglobin (aka clara cell protein) and albumin.
5. In summary, this study utilized a unique approach to chemical vapor exposure in rabbits, to identify HDI reaction products with "self" molecules in the lower airways.</description><identifier>ISSN: 0049-8254</identifier><identifier>ISSN: 1366-5928</identifier><identifier>EISSN: 1366-5928</identifier><identifier>DOI: 10.1080/00498254.2017.1329569</identifier><identifier>PMID: 28489470</identifier><language>eng</language><publisher>England: Taylor & Francis</publisher><subject>Amino Acid Sequence ; Animals ; Body Fluids - metabolism ; Chromatography, Liquid ; Exposure ; glutathione ; hexamethylene diisocyanate ; Isocyanates - pharmacology ; Lung - drug effects ; Male ; Mass Spectrometry ; Models, Molecular ; Molecular Weight ; Peptides - chemistry ; Rabbits ; Tracheostomy ; Volatilization</subject><ispartof>Xenobiotica, 2018-05, Vol.48 (5), p.488-497</ispartof><rights>2017 Informa UK Limited, trading as Taylor & Francis Group. 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c468t-e46a79f0d6e94f71d6dee971c544e08cc38e6084f2e4bfe65a058da37fe791a03</citedby><cites>FETCH-LOGICAL-c468t-e46a79f0d6e94f71d6dee971c544e08cc38e6084f2e4bfe65a058da37fe791a03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28489470$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wisnewski, Adam V.</creatorcontrib><creatorcontrib>Kanyo, Jean</creatorcontrib><creatorcontrib>Asher, Jennifer</creatorcontrib><creatorcontrib>Goodrich, James A.</creatorcontrib><creatorcontrib>Barnett, Grace</creatorcontrib><creatorcontrib>Patrylak, Lyn</creatorcontrib><creatorcontrib>Liu, Jian</creatorcontrib><creatorcontrib>Redlich, Carrie A.</creatorcontrib><creatorcontrib>Nassar, Ala F.</creatorcontrib><title>Reaction products of hexamethylene diisocyanate vapors with "self" molecules in the airways of rabbits exposed via tracheostomy</title><title>Xenobiotica</title><addtitle>Xenobiotica</addtitle><description>1. Hexamethylenediisocyanate (HDI) is a widely used aliphatic diisocyanate and a well-recognized cause of occupational asthma.
2. "Self" molecules (peptides/proteins) in the lower airways, susceptible to chemical reactivity with HDI, have been hypothesized to play a role in asthma pathogenesis and/or chemical metabolism, but remain poorly characterized.
3. This study employed unique approaches to identify and characterize "self" targets of HDI reactivity in the lower airways. Anesthetized rabbits free breathed through a tracheostomy tube connected to chambers containing either, O
2
, or O
2
plus ∼200 ppb HDI vapors. Following 60 minutes of exposure, the airways were lavaged and the fluid was analyzed by LC-MS and LC-MS/MS.
4. The low-molecular weight (<3 kDa) fraction of HDI exposed, but not control rabbit bronchoalveolar lavage (BAL) fluid identified 783.26 and 476.18 m/z [M+H]
+
ions with high energy collision-induced dissociation (HCD) fragmentation patterns consistent with bis glutathione (GSH)-HDI and mono(GSH)-HDI. Proteomic analyses of the high molecular weight (>3 kDa) fraction of exposed rabbit BAL fluid identified HDI modification of specific lysines in uteroglobin (aka clara cell protein) and albumin.
5. In summary, this study utilized a unique approach to chemical vapor exposure in rabbits, to identify HDI reaction products with "self" molecules in the lower airways.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Body Fluids - metabolism</subject><subject>Chromatography, Liquid</subject><subject>Exposure</subject><subject>glutathione</subject><subject>hexamethylene diisocyanate</subject><subject>Isocyanates - pharmacology</subject><subject>Lung - drug effects</subject><subject>Male</subject><subject>Mass Spectrometry</subject><subject>Models, Molecular</subject><subject>Molecular Weight</subject><subject>Peptides - chemistry</subject><subject>Rabbits</subject><subject>Tracheostomy</subject><subject>Volatilization</subject><issn>0049-8254</issn><issn>1366-5928</issn><issn>1366-5928</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp9kc-L1DAUgIMo7rj6JyhhT146Jm2aJhdRFn_BgiB6Dm_SFxtpm5qkM9uT_7odZ3bRi6cc8r3vPfgIec7ZljPFXjEmtCprsS0Zb7a8KnUt9QOy4ZWURa1L9ZBsjkxxhC7Ik5R-MMYkL8vH5KJUQmnRsA359QXBZh9GOsXQzjYnGhzt8BYGzN3S44i09T4Fu8AIGekephATPfjc0auEvbuiQ-jRzj0m6keaO6Tg4wGWP6YIu51fpXg7hYQt3XugOYLtMKQchuUpeeSgT_js_F6Sb-_ffb3-WNx8_vDp-u1NYYVUuUAhodGOtRK1cA1vZYuoG25rIZApayuFkinhShQ7h7IGVqsWqsZhozmw6pK8PnmneTdga3Fcr-jNFP0AcTEBvPn3Z_Sd-R72playKgVfBS_Pghh-zpiyGXyy2PcwYpiT4Uo3ismmrFe0PqE2hpQiuvs1nJljPHMXzxzjmXO8de7F3zfeT93VWoE3J8CPLsQBDiH2rcmw9CG6CKP1yVT_3_EbZ-6ttQ</recordid><startdate>20180504</startdate><enddate>20180504</enddate><creator>Wisnewski, Adam V.</creator><creator>Kanyo, Jean</creator><creator>Asher, Jennifer</creator><creator>Goodrich, James A.</creator><creator>Barnett, Grace</creator><creator>Patrylak, Lyn</creator><creator>Liu, Jian</creator><creator>Redlich, Carrie A.</creator><creator>Nassar, Ala F.</creator><general>Taylor & Francis</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20180504</creationdate><title>Reaction products of hexamethylene diisocyanate vapors with "self" molecules in the airways of rabbits exposed via tracheostomy</title><author>Wisnewski, Adam V. ; Kanyo, Jean ; Asher, Jennifer ; Goodrich, James A. ; Barnett, Grace ; Patrylak, Lyn ; Liu, Jian ; Redlich, Carrie A. ; Nassar, Ala F.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c468t-e46a79f0d6e94f71d6dee971c544e08cc38e6084f2e4bfe65a058da37fe791a03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Body Fluids - metabolism</topic><topic>Chromatography, Liquid</topic><topic>Exposure</topic><topic>glutathione</topic><topic>hexamethylene diisocyanate</topic><topic>Isocyanates - pharmacology</topic><topic>Lung - drug effects</topic><topic>Male</topic><topic>Mass Spectrometry</topic><topic>Models, Molecular</topic><topic>Molecular Weight</topic><topic>Peptides - chemistry</topic><topic>Rabbits</topic><topic>Tracheostomy</topic><topic>Volatilization</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wisnewski, Adam V.</creatorcontrib><creatorcontrib>Kanyo, Jean</creatorcontrib><creatorcontrib>Asher, Jennifer</creatorcontrib><creatorcontrib>Goodrich, James A.</creatorcontrib><creatorcontrib>Barnett, Grace</creatorcontrib><creatorcontrib>Patrylak, Lyn</creatorcontrib><creatorcontrib>Liu, Jian</creatorcontrib><creatorcontrib>Redlich, Carrie A.</creatorcontrib><creatorcontrib>Nassar, Ala F.</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>Xenobiotica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wisnewski, Adam V.</au><au>Kanyo, Jean</au><au>Asher, Jennifer</au><au>Goodrich, James A.</au><au>Barnett, Grace</au><au>Patrylak, Lyn</au><au>Liu, Jian</au><au>Redlich, Carrie A.</au><au>Nassar, Ala F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Reaction products of hexamethylene diisocyanate vapors with "self" molecules in the airways of rabbits exposed via tracheostomy</atitle><jtitle>Xenobiotica</jtitle><addtitle>Xenobiotica</addtitle><date>2018-05-04</date><risdate>2018</risdate><volume>48</volume><issue>5</issue><spage>488</spage><epage>497</epage><pages>488-497</pages><issn>0049-8254</issn><issn>1366-5928</issn><eissn>1366-5928</eissn><abstract>1. Hexamethylenediisocyanate (HDI) is a widely used aliphatic diisocyanate and a well-recognized cause of occupational asthma.
2. "Self" molecules (peptides/proteins) in the lower airways, susceptible to chemical reactivity with HDI, have been hypothesized to play a role in asthma pathogenesis and/or chemical metabolism, but remain poorly characterized.
3. This study employed unique approaches to identify and characterize "self" targets of HDI reactivity in the lower airways. Anesthetized rabbits free breathed through a tracheostomy tube connected to chambers containing either, O
2
, or O
2
plus ∼200 ppb HDI vapors. Following 60 minutes of exposure, the airways were lavaged and the fluid was analyzed by LC-MS and LC-MS/MS.
4. The low-molecular weight (<3 kDa) fraction of HDI exposed, but not control rabbit bronchoalveolar lavage (BAL) fluid identified 783.26 and 476.18 m/z [M+H]
+
ions with high energy collision-induced dissociation (HCD) fragmentation patterns consistent with bis glutathione (GSH)-HDI and mono(GSH)-HDI. Proteomic analyses of the high molecular weight (>3 kDa) fraction of exposed rabbit BAL fluid identified HDI modification of specific lysines in uteroglobin (aka clara cell protein) and albumin.
5. In summary, this study utilized a unique approach to chemical vapor exposure in rabbits, to identify HDI reaction products with "self" molecules in the lower airways.</abstract><cop>England</cop><pub>Taylor & Francis</pub><pmid>28489470</pmid><doi>10.1080/00498254.2017.1329569</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0049-8254 |
| ispartof | Xenobiotica, 2018-05, Vol.48 (5), p.488-497 |
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| language | eng |
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| source | Taylor and Francis:Jisc Collections:Taylor and Francis Read and Publish Agreement 2024-2025:Medical Collection (Reading list) |
| subjects | Amino Acid Sequence Animals Body Fluids - metabolism Chromatography, Liquid Exposure glutathione hexamethylene diisocyanate Isocyanates - pharmacology Lung - drug effects Male Mass Spectrometry Models, Molecular Molecular Weight Peptides - chemistry Rabbits Tracheostomy Volatilization |
| title | Reaction products of hexamethylene diisocyanate vapors with "self" molecules in the airways of rabbits exposed via tracheostomy |
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