Conjugation of nitrated acetaminophen to Der p1 amplifies peripheral blood monocyte response to Der p1
An association of acetaminophen use and asthma was observed in the International Study of Asthma and Allergies in Childhood study. However there are no clear mechanisms to explain an association between acetaminophen use and immunologic pathology. In acidic conditions like those in the stomach and i...
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| Veröffentlicht in: | PloS one 2017-12, Vol.12 (12), p.e0188614-e0188614 |
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| creator | Thomas, Ryan G Rivera Reyes, Brenda M Gaston, Benjamin M Rivera Acosta, Nelki B Bederman, Ilya R Smith, Laura A Sutton, Morgan T Wang, Benlian Hunt, John F Bonfield, Tracey L |
| description | An association of acetaminophen use and asthma was observed in the International Study of Asthma and Allergies in Childhood study. However there are no clear mechanisms to explain an association between acetaminophen use and immunologic pathology. In acidic conditions like those in the stomach and inflamed airway, tyrosine residues are nitrated by nitrous and peroxynitrous acids. The resulting nitrotyrosine is structurally similar to 2,4-dinitrophenol and 2,4-dinitrochlorobenzene, known haptens that enhance immune responses by covalently binding proteins. Nitrated acetaminophen shares similar molecular structure.
We hypothesized the acetaminophen phenol ring undergoes nitration under acidic conditions, producing 3-nitro-acetaminophen which augments allergic responses by acting as a hapten for environmental allergens.
3-nitro-acetaminophen was formed from acetaminophen in the presence of acidified nitrite, purified by high performance liquid chromatography, and assayed by gas-chromatography mass spectrometry. Purified 3-nitro-acetaminophen was reacted with Dermatophagoides pteronyssinus (Der p1) and analyzed by mass spectrometry to identify the modification site. Human peripheral blood mononuclear cells proliferation response was measured in response to 3-nitro-acetaminophen and to 3-nitro-acetaminophen-modified Der p1.
Acetaminophen was modified by nitrous acid forming 3-nitro-acetaminophen over a range of different acidic conditions consistent with airway inflammation and stomach acidity. The Der p1 protein-hapten adduct creation was confirmed by liquid chromatography-mass spectrometry proteomics modifying cysteine 132. Peripheral blood mononuclear cells exposed to 3-nitro-acetaminophen-modified Der p1 had increased proliferation and cytokine production compared to acetaminophen and Der p1 alone (n = 7; p < 0.05).
These data suggests 3-nitro-acetaminophen formation and reaction with Der p1 provides a mechanism by which stomach acid or infection-induced low airway pH in patients could enhance the allergic response to proteins such as Der p1. |
| doi_str_mv | 10.1371/journal.pone.0188614 |
| format | Article |
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We hypothesized the acetaminophen phenol ring undergoes nitration under acidic conditions, producing 3-nitro-acetaminophen which augments allergic responses by acting as a hapten for environmental allergens.
3-nitro-acetaminophen was formed from acetaminophen in the presence of acidified nitrite, purified by high performance liquid chromatography, and assayed by gas-chromatography mass spectrometry. Purified 3-nitro-acetaminophen was reacted with Dermatophagoides pteronyssinus (Der p1) and analyzed by mass spectrometry to identify the modification site. Human peripheral blood mononuclear cells proliferation response was measured in response to 3-nitro-acetaminophen and to 3-nitro-acetaminophen-modified Der p1.
Acetaminophen was modified by nitrous acid forming 3-nitro-acetaminophen over a range of different acidic conditions consistent with airway inflammation and stomach acidity. The Der p1 protein-hapten adduct creation was confirmed by liquid chromatography-mass spectrometry proteomics modifying cysteine 132. Peripheral blood mononuclear cells exposed to 3-nitro-acetaminophen-modified Der p1 had increased proliferation and cytokine production compared to acetaminophen and Der p1 alone (n = 7; p < 0.05).
These data suggests 3-nitro-acetaminophen formation and reaction with Der p1 provides a mechanism by which stomach acid or infection-induced low airway pH in patients could enhance the allergic response to proteins such as Der p1.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0188614</identifier><identifier>PMID: 29228007</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>2,4-Dinitrophenol ; Acetaminophen ; Acetaminophen - chemistry ; Acidification ; Acidity ; Acids ; Allergens ; Allergies ; Analgesics ; Analysis ; Animals ; Antigens, Dermatophagoides - chemistry ; Antigens, Dermatophagoides - immunology ; Arthropod Proteins - chemistry ; Arthropod Proteins - immunology ; Asthma ; Asthma - immunology ; Biology and Life Sciences ; Blood ; Cell proliferation ; Childhood asthma ; Children ; Chromatography ; Conjugation ; Cysteine Endopeptidases - chemistry ; Cysteine Endopeptidases - immunology ; Cystic fibrosis ; Dermatophagoides pteronyssinus - immunology ; Dosage and administration ; Drug therapy ; Fever ; Gas chromatography ; Haptens ; Health aspects ; High performance liquid chromatography ; Humans ; Hypersensitivity ; Immune response ; Inflammation ; International studies ; Leukocytes (mononuclear) ; Liquid chromatography ; Mass spectrometry ; Mass spectroscopy ; Medicine and Health Sciences ; Molecular structure ; Monocytes ; Monocytes - immunology ; Multivariate analysis ; Nitrates - chemistry ; Nitration ; Nitrotyrosine ; Nitrous acid ; Nonsteroidal anti-inflammatory drugs ; p1 Protein ; Pediatrics ; Peripheral blood mononuclear cells ; pH effects ; Phenols ; Physical Sciences ; Protein adducts ; Proteins ; Proteomics ; Research and Analysis Methods ; Respiratory tract ; Respiratory tract diseases ; Spectroscopy ; Stomach ; Studies ; Trends ; Tyrosine</subject><ispartof>PloS one, 2017-12, Vol.12 (12), p.e0188614-e0188614</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Thomas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Thomas et al 2017 Thomas et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-c4a785d1e98905ea00d74174f7e787fb5e4c0321d0ae28082e1fbf3c72fe49473</citedby><cites>FETCH-LOGICAL-c692t-c4a785d1e98905ea00d74174f7e787fb5e4c0321d0ae28082e1fbf3c72fe49473</cites><orcidid>0000-0001-9698-9113 ; 0000-0003-4533-3338</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724819/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5724819/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29228007$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Thomas, Ryan G</creatorcontrib><creatorcontrib>Rivera Reyes, Brenda M</creatorcontrib><creatorcontrib>Gaston, Benjamin M</creatorcontrib><creatorcontrib>Rivera Acosta, Nelki B</creatorcontrib><creatorcontrib>Bederman, Ilya R</creatorcontrib><creatorcontrib>Smith, Laura A</creatorcontrib><creatorcontrib>Sutton, Morgan T</creatorcontrib><creatorcontrib>Wang, Benlian</creatorcontrib><creatorcontrib>Hunt, John F</creatorcontrib><creatorcontrib>Bonfield, Tracey L</creatorcontrib><title>Conjugation of nitrated acetaminophen to Der p1 amplifies peripheral blood monocyte response to Der p1</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>An association of acetaminophen use and asthma was observed in the International Study of Asthma and Allergies in Childhood study. However there are no clear mechanisms to explain an association between acetaminophen use and immunologic pathology. In acidic conditions like those in the stomach and inflamed airway, tyrosine residues are nitrated by nitrous and peroxynitrous acids. The resulting nitrotyrosine is structurally similar to 2,4-dinitrophenol and 2,4-dinitrochlorobenzene, known haptens that enhance immune responses by covalently binding proteins. Nitrated acetaminophen shares similar molecular structure.
We hypothesized the acetaminophen phenol ring undergoes nitration under acidic conditions, producing 3-nitro-acetaminophen which augments allergic responses by acting as a hapten for environmental allergens.
3-nitro-acetaminophen was formed from acetaminophen in the presence of acidified nitrite, purified by high performance liquid chromatography, and assayed by gas-chromatography mass spectrometry. Purified 3-nitro-acetaminophen was reacted with Dermatophagoides pteronyssinus (Der p1) and analyzed by mass spectrometry to identify the modification site. Human peripheral blood mononuclear cells proliferation response was measured in response to 3-nitro-acetaminophen and to 3-nitro-acetaminophen-modified Der p1.
Acetaminophen was modified by nitrous acid forming 3-nitro-acetaminophen over a range of different acidic conditions consistent with airway inflammation and stomach acidity. The Der p1 protein-hapten adduct creation was confirmed by liquid chromatography-mass spectrometry proteomics modifying cysteine 132. Peripheral blood mononuclear cells exposed to 3-nitro-acetaminophen-modified Der p1 had increased proliferation and cytokine production compared to acetaminophen and Der p1 alone (n = 7; p < 0.05).
These data suggests 3-nitro-acetaminophen formation and reaction with Der p1 provides a mechanism by which stomach acid or infection-induced low airway pH in patients could enhance the allergic response to proteins such as Der p1.</description><subject>2,4-Dinitrophenol</subject><subject>Acetaminophen</subject><subject>Acetaminophen - chemistry</subject><subject>Acidification</subject><subject>Acidity</subject><subject>Acids</subject><subject>Allergens</subject><subject>Allergies</subject><subject>Analgesics</subject><subject>Analysis</subject><subject>Animals</subject><subject>Antigens, Dermatophagoides - chemistry</subject><subject>Antigens, Dermatophagoides - immunology</subject><subject>Arthropod Proteins - chemistry</subject><subject>Arthropod Proteins - immunology</subject><subject>Asthma</subject><subject>Asthma - immunology</subject><subject>Biology and Life Sciences</subject><subject>Blood</subject><subject>Cell proliferation</subject><subject>Childhood asthma</subject><subject>Children</subject><subject>Chromatography</subject><subject>Conjugation</subject><subject>Cysteine Endopeptidases - chemistry</subject><subject>Cysteine Endopeptidases - immunology</subject><subject>Cystic fibrosis</subject><subject>Dermatophagoides pteronyssinus - immunology</subject><subject>Dosage and administration</subject><subject>Drug therapy</subject><subject>Fever</subject><subject>Gas chromatography</subject><subject>Haptens</subject><subject>Health aspects</subject><subject>High performance liquid chromatography</subject><subject>Humans</subject><subject>Hypersensitivity</subject><subject>Immune response</subject><subject>Inflammation</subject><subject>International studies</subject><subject>Leukocytes (mononuclear)</subject><subject>Liquid chromatography</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Medicine and Health Sciences</subject><subject>Molecular structure</subject><subject>Monocytes</subject><subject>Monocytes - immunology</subject><subject>Multivariate analysis</subject><subject>Nitrates - chemistry</subject><subject>Nitration</subject><subject>Nitrotyrosine</subject><subject>Nitrous acid</subject><subject>Nonsteroidal anti-inflammatory drugs</subject><subject>p1 Protein</subject><subject>Pediatrics</subject><subject>Peripheral blood mononuclear cells</subject><subject>pH effects</subject><subject>Phenols</subject><subject>Physical Sciences</subject><subject>Protein adducts</subject><subject>Proteins</subject><subject>Proteomics</subject><subject>Research and Analysis Methods</subject><subject>Respiratory tract</subject><subject>Respiratory tract diseases</subject><subject>Spectroscopy</subject><subject>Stomach</subject><subject>Studies</subject><subject>Trends</subject><subject>Tyrosine</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1tvFCEUxydGY-vqNzA6iYnRh12BYYB5MWnW2yZNmnh7JSxz2GXDDFNgjP32st1p7Zo-GB4g8Dv_c-GconiO0QJXHL_b-TH0yi0G38MCYSEYpg-KU9xUZM4Iqh7eOZ8UT2LcIVRXgrHHxQlpCBEI8dPCLH2_GzcqWd-X3pS9TUElaEulIanO9n7YQl8mX36AUA64VN3grLEQywGCzY9BuXLtvG_LzvdeXyUoA8QcVYS_Zk-LR0a5CM-mfVb8-PTx-_LL_Pzi82p5dj7XrCFprqniom4xNKJBNSiEWk4xp4YDF9ysa6AaVQS3SEFOQBDAZm0qzYkB2lBezYqXB93B-SinEkWJG17XguNGZGJ1IFqvdnIItlPhSnpl5fWFDxupQrLagaxpy1rDOGMtpQxIo3GOhasKY8FrobPW-8nbuO6g1dDn4rkj0eOX3m7lxv-SNSdU5N-ZFW8mgeAvR4hJdjZqcE714MfruBlChIk6o6_-Qe_PbqI2Kidge-OzX70XlWc1FlWDGNu7XdxD5dVCZ3XuJ2Pz_ZHB2yODzCT4nTZqjFGuvn39f_bi5zH7-g67BeXSNno37rsxHoP0AOrgYwxgbouMkdyPw0015H4c5DQO2ezF3Q-6Nbrp_-oPTGgEcw</recordid><startdate>20171211</startdate><enddate>20171211</enddate><creator>Thomas, 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of nitrated acetaminophen to Der p1 amplifies peripheral blood monocyte response to Der p1</title><author>Thomas, Ryan G ; Rivera Reyes, Brenda M ; Gaston, Benjamin M ; Rivera Acosta, Nelki B ; Bederman, Ilya R ; Smith, Laura A ; Sutton, Morgan T ; Wang, Benlian ; Hunt, John F ; Bonfield, Tracey L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-c4a785d1e98905ea00d74174f7e787fb5e4c0321d0ae28082e1fbf3c72fe49473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>2,4-Dinitrophenol</topic><topic>Acetaminophen</topic><topic>Acetaminophen - chemistry</topic><topic>Acidification</topic><topic>Acidity</topic><topic>Acids</topic><topic>Allergens</topic><topic>Allergies</topic><topic>Analgesics</topic><topic>Analysis</topic><topic>Animals</topic><topic>Antigens, Dermatophagoides - chemistry</topic><topic>Antigens, Dermatophagoides - immunology</topic><topic>Arthropod Proteins - chemistry</topic><topic>Arthropod Proteins - immunology</topic><topic>Asthma</topic><topic>Asthma - immunology</topic><topic>Biology and Life Sciences</topic><topic>Blood</topic><topic>Cell proliferation</topic><topic>Childhood asthma</topic><topic>Children</topic><topic>Chromatography</topic><topic>Conjugation</topic><topic>Cysteine Endopeptidases - chemistry</topic><topic>Cysteine Endopeptidases - immunology</topic><topic>Cystic fibrosis</topic><topic>Dermatophagoides pteronyssinus - immunology</topic><topic>Dosage and administration</topic><topic>Drug therapy</topic><topic>Fever</topic><topic>Gas chromatography</topic><topic>Haptens</topic><topic>Health aspects</topic><topic>High performance liquid chromatography</topic><topic>Humans</topic><topic>Hypersensitivity</topic><topic>Immune response</topic><topic>Inflammation</topic><topic>International studies</topic><topic>Leukocytes (mononuclear)</topic><topic>Liquid chromatography</topic><topic>Mass spectrometry</topic><topic>Mass 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titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Thomas, Ryan G</au><au>Rivera Reyes, Brenda M</au><au>Gaston, Benjamin M</au><au>Rivera Acosta, Nelki B</au><au>Bederman, Ilya R</au><au>Smith, Laura A</au><au>Sutton, Morgan T</au><au>Wang, Benlian</au><au>Hunt, John F</au><au>Bonfield, Tracey L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Conjugation of nitrated acetaminophen to Der p1 amplifies peripheral blood monocyte response to Der p1</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-12-11</date><risdate>2017</risdate><volume>12</volume><issue>12</issue><spage>e0188614</spage><epage>e0188614</epage><pages>e0188614-e0188614</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>An association of acetaminophen use and asthma was observed in the International Study of Asthma and Allergies in Childhood study. However there are no clear mechanisms to explain an association between acetaminophen use and immunologic pathology. In acidic conditions like those in the stomach and inflamed airway, tyrosine residues are nitrated by nitrous and peroxynitrous acids. The resulting nitrotyrosine is structurally similar to 2,4-dinitrophenol and 2,4-dinitrochlorobenzene, known haptens that enhance immune responses by covalently binding proteins. Nitrated acetaminophen shares similar molecular structure.
We hypothesized the acetaminophen phenol ring undergoes nitration under acidic conditions, producing 3-nitro-acetaminophen which augments allergic responses by acting as a hapten for environmental allergens.
3-nitro-acetaminophen was formed from acetaminophen in the presence of acidified nitrite, purified by high performance liquid chromatography, and assayed by gas-chromatography mass spectrometry. Purified 3-nitro-acetaminophen was reacted with Dermatophagoides pteronyssinus (Der p1) and analyzed by mass spectrometry to identify the modification site. Human peripheral blood mononuclear cells proliferation response was measured in response to 3-nitro-acetaminophen and to 3-nitro-acetaminophen-modified Der p1.
Acetaminophen was modified by nitrous acid forming 3-nitro-acetaminophen over a range of different acidic conditions consistent with airway inflammation and stomach acidity. The Der p1 protein-hapten adduct creation was confirmed by liquid chromatography-mass spectrometry proteomics modifying cysteine 132. Peripheral blood mononuclear cells exposed to 3-nitro-acetaminophen-modified Der p1 had increased proliferation and cytokine production compared to acetaminophen and Der p1 alone (n = 7; p < 0.05).
These data suggests 3-nitro-acetaminophen formation and reaction with Der p1 provides a mechanism by which stomach acid or infection-induced low airway pH in patients could enhance the allergic response to proteins such as Der p1.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29228007</pmid><doi>10.1371/journal.pone.0188614</doi><tpages>e0188614</tpages><orcidid>https://orcid.org/0000-0001-9698-9113</orcidid><orcidid>https://orcid.org/0000-0003-4533-3338</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2017-12, Vol.12 (12), p.e0188614-e0188614 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1975587198 |
| source | PLoS; MEDLINE; DOAJ Directory of Open Access Journals; PubMed Central; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | 2,4-Dinitrophenol Acetaminophen Acetaminophen - chemistry Acidification Acidity Acids Allergens Allergies Analgesics Analysis Animals Antigens, Dermatophagoides - chemistry Antigens, Dermatophagoides - immunology Arthropod Proteins - chemistry Arthropod Proteins - immunology Asthma Asthma - immunology Biology and Life Sciences Blood Cell proliferation Childhood asthma Children Chromatography Conjugation Cysteine Endopeptidases - chemistry Cysteine Endopeptidases - immunology Cystic fibrosis Dermatophagoides pteronyssinus - immunology Dosage and administration Drug therapy Fever Gas chromatography Haptens Health aspects High performance liquid chromatography Humans Hypersensitivity Immune response Inflammation International studies Leukocytes (mononuclear) Liquid chromatography Mass spectrometry Mass spectroscopy Medicine and Health Sciences Molecular structure Monocytes Monocytes - immunology Multivariate analysis Nitrates - chemistry Nitration Nitrotyrosine Nitrous acid Nonsteroidal anti-inflammatory drugs p1 Protein Pediatrics Peripheral blood mononuclear cells pH effects Phenols Physical Sciences Protein adducts Proteins Proteomics Research and Analysis Methods Respiratory tract Respiratory tract diseases Spectroscopy Stomach Studies Trends Tyrosine |
| title | Conjugation of nitrated acetaminophen to Der p1 amplifies peripheral blood monocyte response to Der p1 |
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