Lung collagens perpetuate pulmonary fibrosis via CD204 and M2 macrophage activation
Idiopathic pulmonary fibrosis is characterized by abundant collagen production and accumulation of alternatively activated macrophages (M2) in the lower respiratory tract. Mechanisms as to how alveolar macrophages are activated by collagen breakdown products are unknown. Alveolar macrophages were ob...
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| Veröffentlicht in: | PloS one 2013-11, Vol.8 (11), p.e81382-e81382 |
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| creator | Stahl, Mirjam Schupp, Jonas Jäger, Benedikt Schmid, Michael Zissel, Gernot Müller-Quernheim, Joachim Prasse, Antje |
| description | Idiopathic pulmonary fibrosis is characterized by abundant collagen production and accumulation of alternatively activated macrophages (M2) in the lower respiratory tract. Mechanisms as to how alveolar macrophages are activated by collagen breakdown products are unknown. Alveolar macrophages were obtained by bronchoalveolar lavage from 30 patients with idiopathic pulmonary fibrosis (IPF) and 37 healthy donors (HD). Alveolar macrophages were cultured in the presence of collagen type I, III, IV and V monomers w/wo a neutralizing antibody against scavenger receptor I class A (CD204). Culture supernatants were assayed for the M2 markers CCL18, CCL2, and interleukin-1 receptor antagonist (IL-1ra) by ELISA. Furthermore, expression of phospho-Akt was measured using ELISA and expression of CD204 by RT-PCR and flow cytometry. Stimulation with collagen type I and III monomers significantly up-regulated CCL18, IL-1ra production of alveolar macrophages. Furthermore, expression of CCL2 and CD204 were up-regulated by collagen type I exposure. In addition, collagen type I stimulation increased pospho-Akt expression. Collagen type I effects were abrogated by neutralizing antiCD204 and a non-selective Phosphatidylinositide 3-kinase inhibitor (LY294002). Spontaneous CD204 expression of alveolar macrophages was significantly increased in patients with IPF. In conclusion, our findings demonstrate that monomeric collagen type I via CD204 induces phospho-Akt expression shifting alveolar macrophages to the profibrotic M2 type. Innate immune responses induced by collagen monomers might perpetuate pulmonary fibrosis. |
| doi_str_mv | 10.1371/journal.pone.0081382 |
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Mechanisms as to how alveolar macrophages are activated by collagen breakdown products are unknown. Alveolar macrophages were obtained by bronchoalveolar lavage from 30 patients with idiopathic pulmonary fibrosis (IPF) and 37 healthy donors (HD). Alveolar macrophages were cultured in the presence of collagen type I, III, IV and V monomers w/wo a neutralizing antibody against scavenger receptor I class A (CD204). Culture supernatants were assayed for the M2 markers CCL18, CCL2, and interleukin-1 receptor antagonist (IL-1ra) by ELISA. Furthermore, expression of phospho-Akt was measured using ELISA and expression of CD204 by RT-PCR and flow cytometry. Stimulation with collagen type I and III monomers significantly up-regulated CCL18, IL-1ra production of alveolar macrophages. Furthermore, expression of CCL2 and CD204 were up-regulated by collagen type I exposure. In addition, collagen type I stimulation increased pospho-Akt expression. Collagen type I effects were abrogated by neutralizing antiCD204 and a non-selective Phosphatidylinositide 3-kinase inhibitor (LY294002). Spontaneous CD204 expression of alveolar macrophages was significantly increased in patients with IPF. In conclusion, our findings demonstrate that monomeric collagen type I via CD204 induces phospho-Akt expression shifting alveolar macrophages to the profibrotic M2 type. Innate immune responses induced by collagen monomers might perpetuate pulmonary fibrosis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0081382</identifier><identifier>PMID: 24278429</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>AKT protein ; Alveoli ; Antibodies ; Binding sites ; Bronchus ; Case-Control Studies ; CCL18 protein ; Cell activation ; Chemokine CCL2 - metabolism ; Collagen ; Collagen (type I) ; Collagen - chemistry ; Collagen - metabolism ; Collagen Type I - chemistry ; Collagen Type I - metabolism ; Cytokines ; Cytometry ; Enzyme inhibitors ; Enzyme-linked immunosorbent assay ; Extracellular matrix ; Fibrosis ; Flow cytometry ; Gene Expression ; Humans ; Immune response ; Innate immunity ; Interleukin 1 ; Interleukin 1 receptor antagonist ; Interleukin 1 receptors ; Interleukins ; Kinases ; Laboratories ; Ligands ; Lung - immunology ; Lung - metabolism ; Lung - pathology ; Lung diseases ; Macrophage Activation - immunology ; Macrophages ; Macrophages - immunology ; Macrophages - metabolism ; Macrophages, Alveolar - immunology ; Macrophages, Alveolar - metabolism ; Monocyte chemoattractant protein 1 ; Monomers ; Neutralizing ; Patients ; Phosphatidylinositol 3-Kinases - metabolism ; Phosphorylation ; Polymerase chain reaction ; Proto-Oncogene Proteins c-akt - metabolism ; Pulmonary fibrosis ; Pulmonary Fibrosis - genetics ; Pulmonary Fibrosis - immunology ; Pulmonary Fibrosis - metabolism ; Respiratory tract ; Respiratory tract diseases ; Rodents ; Scavenger receptors ; Scavenger Receptors, Class A - genetics ; Scavenger Receptors, Class A - metabolism ; Signal transduction ; Stimulation ; Tumor necrosis factor-TNF</subject><ispartof>PloS one, 2013-11, Vol.8 (11), p.e81382-e81382</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Stahl et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/3.0/ (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>2013 Stahl et al 2013 Stahl et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-70307d6685aed010a497cf1eb321744bbd3d993f4d8953db0355e236871a52e73</citedby><cites>FETCH-LOGICAL-c692t-70307d6685aed010a497cf1eb321744bbd3d993f4d8953db0355e236871a52e73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3835428/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3835428/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23865,27923,27924,53790,53792,79371,79372</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24278429$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Mora, Ana</contributor><creatorcontrib>Stahl, Mirjam</creatorcontrib><creatorcontrib>Schupp, Jonas</creatorcontrib><creatorcontrib>Jäger, Benedikt</creatorcontrib><creatorcontrib>Schmid, Michael</creatorcontrib><creatorcontrib>Zissel, Gernot</creatorcontrib><creatorcontrib>Müller-Quernheim, Joachim</creatorcontrib><creatorcontrib>Prasse, Antje</creatorcontrib><title>Lung collagens perpetuate pulmonary fibrosis via CD204 and M2 macrophage activation</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Idiopathic pulmonary fibrosis is characterized by abundant collagen production and accumulation of alternatively activated macrophages (M2) in the lower respiratory tract. Mechanisms as to how alveolar macrophages are activated by collagen breakdown products are unknown. Alveolar macrophages were obtained by bronchoalveolar lavage from 30 patients with idiopathic pulmonary fibrosis (IPF) and 37 healthy donors (HD). Alveolar macrophages were cultured in the presence of collagen type I, III, IV and V monomers w/wo a neutralizing antibody against scavenger receptor I class A (CD204). Culture supernatants were assayed for the M2 markers CCL18, CCL2, and interleukin-1 receptor antagonist (IL-1ra) by ELISA. Furthermore, expression of phospho-Akt was measured using ELISA and expression of CD204 by RT-PCR and flow cytometry. Stimulation with collagen type I and III monomers significantly up-regulated CCL18, IL-1ra production of alveolar macrophages. Furthermore, expression of CCL2 and CD204 were up-regulated by collagen type I exposure. In addition, collagen type I stimulation increased pospho-Akt expression. Collagen type I effects were abrogated by neutralizing antiCD204 and a non-selective Phosphatidylinositide 3-kinase inhibitor (LY294002). Spontaneous CD204 expression of alveolar macrophages was significantly increased in patients with IPF. In conclusion, our findings demonstrate that monomeric collagen type I via CD204 induces phospho-Akt expression shifting alveolar macrophages to the profibrotic M2 type. Innate immune responses induced by collagen monomers might perpetuate pulmonary fibrosis.</description><subject>AKT protein</subject><subject>Alveoli</subject><subject>Antibodies</subject><subject>Binding sites</subject><subject>Bronchus</subject><subject>Case-Control Studies</subject><subject>CCL18 protein</subject><subject>Cell activation</subject><subject>Chemokine CCL2 - metabolism</subject><subject>Collagen</subject><subject>Collagen (type I)</subject><subject>Collagen - chemistry</subject><subject>Collagen - metabolism</subject><subject>Collagen Type I - chemistry</subject><subject>Collagen Type I - metabolism</subject><subject>Cytokines</subject><subject>Cytometry</subject><subject>Enzyme inhibitors</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Extracellular matrix</subject><subject>Fibrosis</subject><subject>Flow cytometry</subject><subject>Gene Expression</subject><subject>Humans</subject><subject>Immune response</subject><subject>Innate immunity</subject><subject>Interleukin 1</subject><subject>Interleukin 1 receptor antagonist</subject><subject>Interleukin 1 receptors</subject><subject>Interleukins</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Ligands</subject><subject>Lung - immunology</subject><subject>Lung - metabolism</subject><subject>Lung - pathology</subject><subject>Lung diseases</subject><subject>Macrophage Activation - immunology</subject><subject>Macrophages</subject><subject>Macrophages - immunology</subject><subject>Macrophages - metabolism</subject><subject>Macrophages, Alveolar - immunology</subject><subject>Macrophages, Alveolar - metabolism</subject><subject>Monocyte chemoattractant protein 1</subject><subject>Monomers</subject><subject>Neutralizing</subject><subject>Patients</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphorylation</subject><subject>Polymerase chain reaction</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Pulmonary fibrosis</subject><subject>Pulmonary Fibrosis - genetics</subject><subject>Pulmonary Fibrosis - immunology</subject><subject>Pulmonary Fibrosis - metabolism</subject><subject>Respiratory tract</subject><subject>Respiratory tract diseases</subject><subject>Rodents</subject><subject>Scavenger receptors</subject><subject>Scavenger Receptors, Class A - 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metabolism</topic><topic>Collagen</topic><topic>Collagen (type I)</topic><topic>Collagen - chemistry</topic><topic>Collagen - metabolism</topic><topic>Collagen Type I - chemistry</topic><topic>Collagen Type I - metabolism</topic><topic>Cytokines</topic><topic>Cytometry</topic><topic>Enzyme inhibitors</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Extracellular matrix</topic><topic>Fibrosis</topic><topic>Flow cytometry</topic><topic>Gene Expression</topic><topic>Humans</topic><topic>Immune response</topic><topic>Innate immunity</topic><topic>Interleukin 1</topic><topic>Interleukin 1 receptor antagonist</topic><topic>Interleukin 1 receptors</topic><topic>Interleukins</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Ligands</topic><topic>Lung - immunology</topic><topic>Lung - metabolism</topic><topic>Lung - pathology</topic><topic>Lung diseases</topic><topic>Macrophage Activation - immunology</topic><topic>Macrophages</topic><topic>Macrophages - immunology</topic><topic>Macrophages - 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Academic</collection><collection>PubMed Central (Full Participant 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>Stahl, Mirjam</au><au>Schupp, Jonas</au><au>Jäger, Benedikt</au><au>Schmid, Michael</au><au>Zissel, Gernot</au><au>Müller-Quernheim, Joachim</au><au>Prasse, Antje</au><au>Mora, Ana</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lung collagens perpetuate pulmonary fibrosis via CD204 and M2 macrophage activation</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-11-20</date><risdate>2013</risdate><volume>8</volume><issue>11</issue><spage>e81382</spage><epage>e81382</epage><pages>e81382-e81382</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Idiopathic pulmonary fibrosis is characterized by abundant collagen production and accumulation of alternatively activated macrophages (M2) in the lower respiratory tract. Mechanisms as to how alveolar macrophages are activated by collagen breakdown products are unknown. Alveolar macrophages were obtained by bronchoalveolar lavage from 30 patients with idiopathic pulmonary fibrosis (IPF) and 37 healthy donors (HD). Alveolar macrophages were cultured in the presence of collagen type I, III, IV and V monomers w/wo a neutralizing antibody against scavenger receptor I class A (CD204). Culture supernatants were assayed for the M2 markers CCL18, CCL2, and interleukin-1 receptor antagonist (IL-1ra) by ELISA. Furthermore, expression of phospho-Akt was measured using ELISA and expression of CD204 by RT-PCR and flow cytometry. Stimulation with collagen type I and III monomers significantly up-regulated CCL18, IL-1ra production of alveolar macrophages. Furthermore, expression of CCL2 and CD204 were up-regulated by collagen type I exposure. In addition, collagen type I stimulation increased pospho-Akt expression. Collagen type I effects were abrogated by neutralizing antiCD204 and a non-selective Phosphatidylinositide 3-kinase inhibitor (LY294002). Spontaneous CD204 expression of alveolar macrophages was significantly increased in patients with IPF. In conclusion, our findings demonstrate that monomeric collagen type I via CD204 induces phospho-Akt expression shifting alveolar macrophages to the profibrotic M2 type. Innate immune responses induced by collagen monomers might perpetuate pulmonary fibrosis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24278429</pmid><doi>10.1371/journal.pone.0081382</doi><tpages>e81382</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1460160751 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | AKT protein Alveoli Antibodies Binding sites Bronchus Case-Control Studies CCL18 protein Cell activation Chemokine CCL2 - metabolism Collagen Collagen (type I) Collagen - chemistry Collagen - metabolism Collagen Type I - chemistry Collagen Type I - metabolism Cytokines Cytometry Enzyme inhibitors Enzyme-linked immunosorbent assay Extracellular matrix Fibrosis Flow cytometry Gene Expression Humans Immune response Innate immunity Interleukin 1 Interleukin 1 receptor antagonist Interleukin 1 receptors Interleukins Kinases Laboratories Ligands Lung - immunology Lung - metabolism Lung - pathology Lung diseases Macrophage Activation - immunology Macrophages Macrophages - immunology Macrophages - metabolism Macrophages, Alveolar - immunology Macrophages, Alveolar - metabolism Monocyte chemoattractant protein 1 Monomers Neutralizing Patients Phosphatidylinositol 3-Kinases - metabolism Phosphorylation Polymerase chain reaction Proto-Oncogene Proteins c-akt - metabolism Pulmonary fibrosis Pulmonary Fibrosis - genetics Pulmonary Fibrosis - immunology Pulmonary Fibrosis - metabolism Respiratory tract Respiratory tract diseases Rodents Scavenger receptors Scavenger Receptors, Class A - genetics Scavenger Receptors, Class A - metabolism Signal transduction Stimulation Tumor necrosis factor-TNF |
| title | Lung collagens perpetuate pulmonary fibrosis via CD204 and M2 macrophage activation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-12T20%3A29%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Lung%20collagens%20perpetuate%20pulmonary%20fibrosis%20via%20CD204%20and%20M2%20macrophage%20activation&rft.jtitle=PloS%20one&rft.au=Stahl,%20Mirjam&rft.date=2013-11-20&rft.volume=8&rft.issue=11&rft.spage=e81382&rft.epage=e81382&rft.pages=e81382-e81382&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0081382&rft_dat=%3Cgale_plos_%3EA478186286%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1460160751&rft_id=info:pmid/24278429&rft_galeid=A478186286&rft_doaj_id=oai_doaj_org_article_3d3a7362be2d4a44a0c34060639c3e6c&rfr_iscdi=true |