DEL‐1, as an anti‐neutrophil transepithelial migration molecule, inhibits airway neutrophilic inflammation in asthma
Background Neutrophil migration into the airways is a key process in neutrophilic asthma. Developmental endothelial locus‐1 (DEL‐1), an extracellular matrix protein, is a neutrophil adhesion inhibitor that attenuates neutrophilic inflammation. Methods Levels of DEL‐1 were measured in exhaled breath...
Gespeichert in:
| Veröffentlicht in: | Allergy (Copenhagen) 2024-05, Vol.79 (5), p.1180-1194 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1194 |
|---|---|
| container_issue | 5 |
| container_start_page | 1180 |
| container_title | Allergy (Copenhagen) |
| container_volume | 79 |
| creator | Jia, Man Fu, Heng Jiang, Xinyu Wang, Lina Xu, Jiayan Barnes, Peter J. Adcock, Ian M. Liu, Yi He, Shujuan Zhang, Fan Yao, Lei Sun, Peng Yao, Xin |
| description | Background
Neutrophil migration into the airways is a key process in neutrophilic asthma. Developmental endothelial locus‐1 (DEL‐1), an extracellular matrix protein, is a neutrophil adhesion inhibitor that attenuates neutrophilic inflammation.
Methods
Levels of DEL‐1 were measured in exhaled breath condensate (EBC) and serum in asthma patients by ELISA. DEL‐1 modulation of neutrophil adhesion and transepithelial migration was examined in a co‐culture model in vitro. The effects of DEL‐1‐adenoviral vector‐mediated overexpression on ovalbumin/lipopolysaccharide (OVA/LPS)‐induced neutrophilic asthma were studied in mice in vivo.
Results
DEL‐1 was primarily expressed in human bronchial epithelial cells and was decreased in asthma patients. Serum DEL‐1 concentrations were reduced in patients with severe asthma compared with normal subjects (567.1 ± 75.3 vs. 276.8 ± 29.36 pg/mL, p |
| doi_str_mv | 10.1111/all.15882 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2863301817</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3049087620</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3882-57816b870dad1d347934c6033b57d6dacf2553cff470a2fb1a4da6782a4765e43</originalsourceid><addsrcrecordid>eNp1kctKxDAUhoMoOl4WvoAU3CjYMWmaJlmKdyi40XU4bVMnkrZj0jLOzkfwGX0Sox0VBEMghHznO0l-hPYJnpIwTsHaKWFCJGtoQqgUsZSSraMJJpjFKaNiC217_4Qx5onEm2iL8kyQRMoJerm4zN9f38hJBD6CNszehH2rh95185mxUe-g9Xpu-pm2BmzUmEcHvenaqOmsLgerTyLTzkxh-mAwbgHL6LfclOGwttA0Y40JLXw_a2AXbdRgvd5brTvo4ery_vwmzu-ub8_P8rik4UEx44JkheC4gopUNOWSpmWGKS0Yr7IKyjphjJZ1nXIMSV0QSCvIuEgg5RnTKd1BR6N37rrnQfteNcaX2lpodTd4lYiMUkwE4QE9_IM-dYNrw-0UxanEgmcJDtTxSJWu897pWs2dacAtFcHqMw4V4lBfcQT2YGUcikZXP-T3_wfgdAQWxurl_yZ1luej8gMBJ5bA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3049087620</pqid></control><display><type>article</type><title>DEL‐1, as an anti‐neutrophil transepithelial migration molecule, inhibits airway neutrophilic inflammation in asthma</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Jia, Man ; Fu, Heng ; Jiang, Xinyu ; Wang, Lina ; Xu, Jiayan ; Barnes, Peter J. ; Adcock, Ian M. ; Liu, Yi ; He, Shujuan ; Zhang, Fan ; Yao, Lei ; Sun, Peng ; Yao, Xin</creator><creatorcontrib>Jia, Man ; Fu, Heng ; Jiang, Xinyu ; Wang, Lina ; Xu, Jiayan ; Barnes, Peter J. ; Adcock, Ian M. ; Liu, Yi ; He, Shujuan ; Zhang, Fan ; Yao, Lei ; Sun, Peng ; Yao, Xin</creatorcontrib><description>Background
Neutrophil migration into the airways is a key process in neutrophilic asthma. Developmental endothelial locus‐1 (DEL‐1), an extracellular matrix protein, is a neutrophil adhesion inhibitor that attenuates neutrophilic inflammation.
Methods
Levels of DEL‐1 were measured in exhaled breath condensate (EBC) and serum in asthma patients by ELISA. DEL‐1 modulation of neutrophil adhesion and transepithelial migration was examined in a co‐culture model in vitro. The effects of DEL‐1‐adenoviral vector‐mediated overexpression on ovalbumin/lipopolysaccharide (OVA/LPS)‐induced neutrophilic asthma were studied in mice in vivo.
Results
DEL‐1 was primarily expressed in human bronchial epithelial cells and was decreased in asthma patients. Serum DEL‐1 concentrations were reduced in patients with severe asthma compared with normal subjects (567.1 ± 75.3 vs. 276.8 ± 29.36 pg/mL, p < .001) and were negatively correlated to blood neutrophils (r = −0.2881, p = .0384) and neutrophil‐to‐lymphocyte ratio (NLR) (r = −0.5469, p < .0001). DEL‐1 concentrations in the EBC of severe asthmatic patients (113.2 ± 8.09 pg/mL) were also lower than normal subjects (193.0 ± 7.61 pg/mL, p < .001) and were positively correlated with the asthma control test (ACT) score (r = 0.3678, p = .0035) and negatively related to EBC IL‐17 (r = −0.3756, p = .0131), myeloperoxidase (MPO) (r = −0.5967, p = .0055), and neutrophil elastase (NE) (r = −0.5488, p = .0009) expression in asthma patients. Neutrophil adhesion and transepithelial migration in asthma patients were associated with LFA‐1 binding to ICAM‐1 and inhibited by DEL‐1. DEL‐1 mRNA and protein expression in human bronchial epithelial cells were regulated by IL‐17. Exogenous DEL‐1 inhibited IL‐17‐enhanced neutrophil adhesion and migration. DEL‐1 expression was decreased while neutrophil infiltration was increased in the airway of a murine model of neutrophilic asthma. This was prevented by DEL‐1 overexpression.
Conclusions
DEL‐1 down‐regulation leads to increased neutrophil migration across bronchial epithelial cells and is associated with neutrophilic airway inflammation in asthma.
EBC and serum DEL‐1 levels are decreased in asthma and are correlated with neutrophil related markers. IL‐17 induces downregulation of DEL‐1 in 16HBE, whereas exogenous DEL‐1 significantly suppresses IL‐17‐induced neutrophil adhesion and transepithelial migration in asthma. DEL‐1 overexpression attenuates airway neutrophil infiltration in neutrophilic asthmatic mice.Abbreviations: 16HBE, human bronchial epithelial cell line; AAV, adeno‐associated virus; AHR, airway hyperresponsiveness; DEL‐1, developmental endothelial locus‐1; EBC, exhaled breath condensate; IL‐17, interleukin 17; LPS, lipopolysaccharide; Ly6G, lymphocyte antigen 6 family member G; MPO, myeloperoxidase; NE, neutrophil elastase; NLR, neutrophil‐to‐leukocyte ratio; OVA, ovalbumin; WBC, white blood cells.</description><identifier>ISSN: 0105-4538</identifier><identifier>ISSN: 1398-9995</identifier><identifier>EISSN: 1398-9995</identifier><identifier>DOI: 10.1111/all.15882</identifier><identifier>PMID: 37681299</identifier><language>eng</language><publisher>Denmark: Blackwell Publishing Ltd</publisher><subject>Adult ; Animal models ; Animals ; Asthma ; Asthma - immunology ; Asthma - metabolism ; bronchial epithelial cells ; Calcium-Binding Proteins - metabolism ; Cell Adhesion ; Cell Adhesion Molecules - metabolism ; Cell culture ; DEL‐1 ; Disease Models, Animal ; Elastase ; Epithelial cells ; Extracellular matrix ; Female ; Gene expression ; Humans ; Inflammation ; Inflammation - immunology ; Inflammation - metabolism ; Leukocyte migration ; Leukocytes (neutrophilic) ; Lipopolysaccharides ; Lymphocytes ; Male ; Matrix protein ; Mice ; Middle Aged ; mRNA ; neutrophil transepithelial migration ; Neutrophils ; Neutrophils - immunology ; Neutrophils - metabolism ; Ovalbumin ; Peroxidase ; Respiratory tract diseases ; Transendothelial and Transepithelial Migration</subject><ispartof>Allergy (Copenhagen), 2024-05, Vol.79 (5), p.1180-1194</ispartof><rights>2023 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.</rights><rights>Copyright © 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3882-57816b870dad1d347934c6033b57d6dacf2553cff470a2fb1a4da6782a4765e43</citedby><cites>FETCH-LOGICAL-c3882-57816b870dad1d347934c6033b57d6dacf2553cff470a2fb1a4da6782a4765e43</cites><orcidid>0000-0003-2101-8843 ; 0000-0002-4578-3673 ; 0000-0002-1455-7358 ; 0009-0009-9969-6557 ; 0000-0002-5122-4018 ; 0000-0002-3682-6432</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fall.15882$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fall.15882$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37681299$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jia, Man</creatorcontrib><creatorcontrib>Fu, Heng</creatorcontrib><creatorcontrib>Jiang, Xinyu</creatorcontrib><creatorcontrib>Wang, Lina</creatorcontrib><creatorcontrib>Xu, Jiayan</creatorcontrib><creatorcontrib>Barnes, Peter J.</creatorcontrib><creatorcontrib>Adcock, Ian M.</creatorcontrib><creatorcontrib>Liu, Yi</creatorcontrib><creatorcontrib>He, Shujuan</creatorcontrib><creatorcontrib>Zhang, Fan</creatorcontrib><creatorcontrib>Yao, Lei</creatorcontrib><creatorcontrib>Sun, Peng</creatorcontrib><creatorcontrib>Yao, Xin</creatorcontrib><title>DEL‐1, as an anti‐neutrophil transepithelial migration molecule, inhibits airway neutrophilic inflammation in asthma</title><title>Allergy (Copenhagen)</title><addtitle>Allergy</addtitle><description>Background
Neutrophil migration into the airways is a key process in neutrophilic asthma. Developmental endothelial locus‐1 (DEL‐1), an extracellular matrix protein, is a neutrophil adhesion inhibitor that attenuates neutrophilic inflammation.
Methods
Levels of DEL‐1 were measured in exhaled breath condensate (EBC) and serum in asthma patients by ELISA. DEL‐1 modulation of neutrophil adhesion and transepithelial migration was examined in a co‐culture model in vitro. The effects of DEL‐1‐adenoviral vector‐mediated overexpression on ovalbumin/lipopolysaccharide (OVA/LPS)‐induced neutrophilic asthma were studied in mice in vivo.
Results
DEL‐1 was primarily expressed in human bronchial epithelial cells and was decreased in asthma patients. Serum DEL‐1 concentrations were reduced in patients with severe asthma compared with normal subjects (567.1 ± 75.3 vs. 276.8 ± 29.36 pg/mL, p < .001) and were negatively correlated to blood neutrophils (r = −0.2881, p = .0384) and neutrophil‐to‐lymphocyte ratio (NLR) (r = −0.5469, p < .0001). DEL‐1 concentrations in the EBC of severe asthmatic patients (113.2 ± 8.09 pg/mL) were also lower than normal subjects (193.0 ± 7.61 pg/mL, p < .001) and were positively correlated with the asthma control test (ACT) score (r = 0.3678, p = .0035) and negatively related to EBC IL‐17 (r = −0.3756, p = .0131), myeloperoxidase (MPO) (r = −0.5967, p = .0055), and neutrophil elastase (NE) (r = −0.5488, p = .0009) expression in asthma patients. Neutrophil adhesion and transepithelial migration in asthma patients were associated with LFA‐1 binding to ICAM‐1 and inhibited by DEL‐1. DEL‐1 mRNA and protein expression in human bronchial epithelial cells were regulated by IL‐17. Exogenous DEL‐1 inhibited IL‐17‐enhanced neutrophil adhesion and migration. DEL‐1 expression was decreased while neutrophil infiltration was increased in the airway of a murine model of neutrophilic asthma. This was prevented by DEL‐1 overexpression.
Conclusions
DEL‐1 down‐regulation leads to increased neutrophil migration across bronchial epithelial cells and is associated with neutrophilic airway inflammation in asthma.
EBC and serum DEL‐1 levels are decreased in asthma and are correlated with neutrophil related markers. IL‐17 induces downregulation of DEL‐1 in 16HBE, whereas exogenous DEL‐1 significantly suppresses IL‐17‐induced neutrophil adhesion and transepithelial migration in asthma. DEL‐1 overexpression attenuates airway neutrophil infiltration in neutrophilic asthmatic mice.Abbreviations: 16HBE, human bronchial epithelial cell line; AAV, adeno‐associated virus; AHR, airway hyperresponsiveness; DEL‐1, developmental endothelial locus‐1; EBC, exhaled breath condensate; IL‐17, interleukin 17; LPS, lipopolysaccharide; Ly6G, lymphocyte antigen 6 family member G; MPO, myeloperoxidase; NE, neutrophil elastase; NLR, neutrophil‐to‐leukocyte ratio; OVA, ovalbumin; WBC, white blood cells.</description><subject>Adult</subject><subject>Animal models</subject><subject>Animals</subject><subject>Asthma</subject><subject>Asthma - immunology</subject><subject>Asthma - metabolism</subject><subject>bronchial epithelial cells</subject><subject>Calcium-Binding Proteins - metabolism</subject><subject>Cell Adhesion</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Cell culture</subject><subject>DEL‐1</subject><subject>Disease Models, Animal</subject><subject>Elastase</subject><subject>Epithelial cells</subject><subject>Extracellular matrix</subject><subject>Female</subject><subject>Gene expression</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Inflammation - immunology</subject><subject>Inflammation - metabolism</subject><subject>Leukocyte migration</subject><subject>Leukocytes (neutrophilic)</subject><subject>Lipopolysaccharides</subject><subject>Lymphocytes</subject><subject>Male</subject><subject>Matrix protein</subject><subject>Mice</subject><subject>Middle Aged</subject><subject>mRNA</subject><subject>neutrophil transepithelial migration</subject><subject>Neutrophils</subject><subject>Neutrophils - immunology</subject><subject>Neutrophils - metabolism</subject><subject>Ovalbumin</subject><subject>Peroxidase</subject><subject>Respiratory tract diseases</subject><subject>Transendothelial and Transepithelial Migration</subject><issn>0105-4538</issn><issn>1398-9995</issn><issn>1398-9995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kctKxDAUhoMoOl4WvoAU3CjYMWmaJlmKdyi40XU4bVMnkrZj0jLOzkfwGX0Sox0VBEMghHznO0l-hPYJnpIwTsHaKWFCJGtoQqgUsZSSraMJJpjFKaNiC217_4Qx5onEm2iL8kyQRMoJerm4zN9f38hJBD6CNszehH2rh95185mxUe-g9Xpu-pm2BmzUmEcHvenaqOmsLgerTyLTzkxh-mAwbgHL6LfclOGwttA0Y40JLXw_a2AXbdRgvd5brTvo4ery_vwmzu-ub8_P8rik4UEx44JkheC4gopUNOWSpmWGKS0Yr7IKyjphjJZ1nXIMSV0QSCvIuEgg5RnTKd1BR6N37rrnQfteNcaX2lpodTd4lYiMUkwE4QE9_IM-dYNrw-0UxanEgmcJDtTxSJWu897pWs2dacAtFcHqMw4V4lBfcQT2YGUcikZXP-T3_wfgdAQWxurl_yZ1luej8gMBJ5bA</recordid><startdate>202405</startdate><enddate>202405</enddate><creator>Jia, Man</creator><creator>Fu, Heng</creator><creator>Jiang, Xinyu</creator><creator>Wang, Lina</creator><creator>Xu, Jiayan</creator><creator>Barnes, Peter J.</creator><creator>Adcock, Ian M.</creator><creator>Liu, Yi</creator><creator>He, Shujuan</creator><creator>Zhang, Fan</creator><creator>Yao, Lei</creator><creator>Sun, Peng</creator><creator>Yao, Xin</creator><general>Blackwell Publishing Ltd</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>7T5</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-2101-8843</orcidid><orcidid>https://orcid.org/0000-0002-4578-3673</orcidid><orcidid>https://orcid.org/0000-0002-1455-7358</orcidid><orcidid>https://orcid.org/0009-0009-9969-6557</orcidid><orcidid>https://orcid.org/0000-0002-5122-4018</orcidid><orcidid>https://orcid.org/0000-0002-3682-6432</orcidid></search><sort><creationdate>202405</creationdate><title>DEL‐1, as an anti‐neutrophil transepithelial migration molecule, inhibits airway neutrophilic inflammation in asthma</title><author>Jia, Man ; Fu, Heng ; Jiang, Xinyu ; Wang, Lina ; Xu, Jiayan ; Barnes, Peter J. ; Adcock, Ian M. ; Liu, Yi ; He, Shujuan ; Zhang, Fan ; Yao, Lei ; Sun, Peng ; Yao, Xin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3882-57816b870dad1d347934c6033b57d6dacf2553cff470a2fb1a4da6782a4765e43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Animal models</topic><topic>Animals</topic><topic>Asthma</topic><topic>Asthma - immunology</topic><topic>Asthma - metabolism</topic><topic>bronchial epithelial cells</topic><topic>Calcium-Binding Proteins - metabolism</topic><topic>Cell Adhesion</topic><topic>Cell Adhesion Molecules - metabolism</topic><topic>Cell culture</topic><topic>DEL‐1</topic><topic>Disease Models, Animal</topic><topic>Elastase</topic><topic>Epithelial cells</topic><topic>Extracellular matrix</topic><topic>Female</topic><topic>Gene expression</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Inflammation - immunology</topic><topic>Inflammation - metabolism</topic><topic>Leukocyte migration</topic><topic>Leukocytes (neutrophilic)</topic><topic>Lipopolysaccharides</topic><topic>Lymphocytes</topic><topic>Male</topic><topic>Matrix protein</topic><topic>Mice</topic><topic>Middle Aged</topic><topic>mRNA</topic><topic>neutrophil transepithelial migration</topic><topic>Neutrophils</topic><topic>Neutrophils - immunology</topic><topic>Neutrophils - metabolism</topic><topic>Ovalbumin</topic><topic>Peroxidase</topic><topic>Respiratory tract diseases</topic><topic>Transendothelial and Transepithelial Migration</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jia, Man</creatorcontrib><creatorcontrib>Fu, Heng</creatorcontrib><creatorcontrib>Jiang, Xinyu</creatorcontrib><creatorcontrib>Wang, Lina</creatorcontrib><creatorcontrib>Xu, Jiayan</creatorcontrib><creatorcontrib>Barnes, Peter J.</creatorcontrib><creatorcontrib>Adcock, Ian M.</creatorcontrib><creatorcontrib>Liu, Yi</creatorcontrib><creatorcontrib>He, Shujuan</creatorcontrib><creatorcontrib>Zhang, Fan</creatorcontrib><creatorcontrib>Yao, Lei</creatorcontrib><creatorcontrib>Sun, Peng</creatorcontrib><creatorcontrib>Yao, Xin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Allergy (Copenhagen)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jia, Man</au><au>Fu, Heng</au><au>Jiang, Xinyu</au><au>Wang, Lina</au><au>Xu, Jiayan</au><au>Barnes, Peter J.</au><au>Adcock, Ian M.</au><au>Liu, Yi</au><au>He, Shujuan</au><au>Zhang, Fan</au><au>Yao, Lei</au><au>Sun, Peng</au><au>Yao, Xin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DEL‐1, as an anti‐neutrophil transepithelial migration molecule, inhibits airway neutrophilic inflammation in asthma</atitle><jtitle>Allergy (Copenhagen)</jtitle><addtitle>Allergy</addtitle><date>2024-05</date><risdate>2024</risdate><volume>79</volume><issue>5</issue><spage>1180</spage><epage>1194</epage><pages>1180-1194</pages><issn>0105-4538</issn><issn>1398-9995</issn><eissn>1398-9995</eissn><abstract>Background
Neutrophil migration into the airways is a key process in neutrophilic asthma. Developmental endothelial locus‐1 (DEL‐1), an extracellular matrix protein, is a neutrophil adhesion inhibitor that attenuates neutrophilic inflammation.
Methods
Levels of DEL‐1 were measured in exhaled breath condensate (EBC) and serum in asthma patients by ELISA. DEL‐1 modulation of neutrophil adhesion and transepithelial migration was examined in a co‐culture model in vitro. The effects of DEL‐1‐adenoviral vector‐mediated overexpression on ovalbumin/lipopolysaccharide (OVA/LPS)‐induced neutrophilic asthma were studied in mice in vivo.
Results
DEL‐1 was primarily expressed in human bronchial epithelial cells and was decreased in asthma patients. Serum DEL‐1 concentrations were reduced in patients with severe asthma compared with normal subjects (567.1 ± 75.3 vs. 276.8 ± 29.36 pg/mL, p < .001) and were negatively correlated to blood neutrophils (r = −0.2881, p = .0384) and neutrophil‐to‐lymphocyte ratio (NLR) (r = −0.5469, p < .0001). DEL‐1 concentrations in the EBC of severe asthmatic patients (113.2 ± 8.09 pg/mL) were also lower than normal subjects (193.0 ± 7.61 pg/mL, p < .001) and were positively correlated with the asthma control test (ACT) score (r = 0.3678, p = .0035) and negatively related to EBC IL‐17 (r = −0.3756, p = .0131), myeloperoxidase (MPO) (r = −0.5967, p = .0055), and neutrophil elastase (NE) (r = −0.5488, p = .0009) expression in asthma patients. Neutrophil adhesion and transepithelial migration in asthma patients were associated with LFA‐1 binding to ICAM‐1 and inhibited by DEL‐1. DEL‐1 mRNA and protein expression in human bronchial epithelial cells were regulated by IL‐17. Exogenous DEL‐1 inhibited IL‐17‐enhanced neutrophil adhesion and migration. DEL‐1 expression was decreased while neutrophil infiltration was increased in the airway of a murine model of neutrophilic asthma. This was prevented by DEL‐1 overexpression.
Conclusions
DEL‐1 down‐regulation leads to increased neutrophil migration across bronchial epithelial cells and is associated with neutrophilic airway inflammation in asthma.
EBC and serum DEL‐1 levels are decreased in asthma and are correlated with neutrophil related markers. IL‐17 induces downregulation of DEL‐1 in 16HBE, whereas exogenous DEL‐1 significantly suppresses IL‐17‐induced neutrophil adhesion and transepithelial migration in asthma. DEL‐1 overexpression attenuates airway neutrophil infiltration in neutrophilic asthmatic mice.Abbreviations: 16HBE, human bronchial epithelial cell line; AAV, adeno‐associated virus; AHR, airway hyperresponsiveness; DEL‐1, developmental endothelial locus‐1; EBC, exhaled breath condensate; IL‐17, interleukin 17; LPS, lipopolysaccharide; Ly6G, lymphocyte antigen 6 family member G; MPO, myeloperoxidase; NE, neutrophil elastase; NLR, neutrophil‐to‐leukocyte ratio; OVA, ovalbumin; WBC, white blood cells.</abstract><cop>Denmark</cop><pub>Blackwell Publishing Ltd</pub><pmid>37681299</pmid><doi>10.1111/all.15882</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0003-2101-8843</orcidid><orcidid>https://orcid.org/0000-0002-4578-3673</orcidid><orcidid>https://orcid.org/0000-0002-1455-7358</orcidid><orcidid>https://orcid.org/0009-0009-9969-6557</orcidid><orcidid>https://orcid.org/0000-0002-5122-4018</orcidid><orcidid>https://orcid.org/0000-0002-3682-6432</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0105-4538 |
| ispartof | Allergy (Copenhagen), 2024-05, Vol.79 (5), p.1180-1194 |
| issn | 0105-4538 1398-9995 1398-9995 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2863301817 |
| source | MEDLINE; Wiley Online Library Journals Frontfile Complete |
| subjects | Adult Animal models Animals Asthma Asthma - immunology Asthma - metabolism bronchial epithelial cells Calcium-Binding Proteins - metabolism Cell Adhesion Cell Adhesion Molecules - metabolism Cell culture DEL‐1 Disease Models, Animal Elastase Epithelial cells Extracellular matrix Female Gene expression Humans Inflammation Inflammation - immunology Inflammation - metabolism Leukocyte migration Leukocytes (neutrophilic) Lipopolysaccharides Lymphocytes Male Matrix protein Mice Middle Aged mRNA neutrophil transepithelial migration Neutrophils Neutrophils - immunology Neutrophils - metabolism Ovalbumin Peroxidase Respiratory tract diseases Transendothelial and Transepithelial Migration |
| title | DEL‐1, as an anti‐neutrophil transepithelial migration molecule, inhibits airway neutrophilic inflammation in asthma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-02T06%3A21%3A17IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=DEL%E2%80%901,%20as%20an%20anti%E2%80%90neutrophil%20transepithelial%20migration%20molecule,%20inhibits%20airway%20neutrophilic%20inflammation%20in%20asthma&rft.jtitle=Allergy%20(Copenhagen)&rft.au=Jia,%20Man&rft.date=2024-05&rft.volume=79&rft.issue=5&rft.spage=1180&rft.epage=1194&rft.pages=1180-1194&rft.issn=0105-4538&rft.eissn=1398-9995&rft_id=info:doi/10.1111/all.15882&rft_dat=%3Cproquest_cross%3E3049087620%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3049087620&rft_id=info:pmid/37681299&rfr_iscdi=true |