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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Autores principales:	Mirjam Stahl, Jonas Schupp, Benedikt Jäger, Michael Schmid, Gernot Zissel, Joachim Müller-Quernheim, Antje Prasse
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3d3a7362be2d4a44a0c34060639c3e6c
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spelling	oai:doaj.org-article:3d3a7362be2d4a44a0c34060639c3e6c2021-11-18T08:45:22ZLung collagens perpetuate pulmonary fibrosis via CD204 and M2 macrophage activation.1932-620310.1371/journal.pone.0081382https://doaj.org/article/3d3a7362be2d4a44a0c34060639c3e6c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24278429/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Idiopathic 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.Mirjam StahlJonas SchuppBenedikt JägerMichael SchmidGernot ZisselJoachim Müller-QuernheimAntje PrassePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 11, p e81382 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mirjam Stahl Jonas Schupp Benedikt Jäger Michael Schmid Gernot Zissel Joachim Müller-Quernheim Antje Prasse Lung collagens perpetuate pulmonary fibrosis via CD204 and M2 macrophage activation.
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.
format	article
author	Mirjam Stahl Jonas Schupp Benedikt Jäger Michael Schmid Gernot Zissel Joachim Müller-Quernheim Antje Prasse
author_facet	Mirjam Stahl Jonas Schupp Benedikt Jäger Michael Schmid Gernot Zissel Joachim Müller-Quernheim Antje Prasse
author_sort	Mirjam Stahl
title	Lung collagens perpetuate pulmonary fibrosis via CD204 and M2 macrophage activation.
title_short	Lung collagens perpetuate pulmonary fibrosis via CD204 and M2 macrophage activation.
title_full	Lung collagens perpetuate pulmonary fibrosis via CD204 and M2 macrophage activation.
title_fullStr	Lung collagens perpetuate pulmonary fibrosis via CD204 and M2 macrophage activation.
title_full_unstemmed	Lung collagens perpetuate pulmonary fibrosis via CD204 and M2 macrophage activation.
title_sort	lung collagens perpetuate pulmonary fibrosis via cd204 and m2 macrophage activation.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/3d3a7362be2d4a44a0c34060639c3e6c
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Lung collagens perpetuate pulmonary fibrosis via CD204 and M2 macrophage activation.

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