Collagen 1a1 Expression by Airway Macrophages Increases In Fibrotic ILDs and Is Associated With FVC Decline and Increased Mortality

Within the Interstitial Lung Diseases (ILD), patients with idiopathic pulmonary fibrosis (IPF) and a subset of those with non-IPF fibrotic ILD have a distinct clinical phenotype of progression despite management. This group of patients has been collectively termed the progressive fibrotic phenotype...

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Autores principales:	Eliza Tsitoura, Athina Trachalaki, Eirini Vasarmidi, Semeli Mastrodemou, George A. Margaritopoulos, Maria Kokosi, Dionysios Fanidis, Apostolos Galaris, Vassilis Aidinis, Elizabeth Renzoni, Nikos Tzanakis, Athol U. Wells, Katerina M. Antoniou
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	IPF RA-ILD NSIP airway macrophages SPP1 osteopontin Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/db8b3a2a2f2d4bf09d7b6d455f17bed9
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spelling	oai:doaj.org-article:db8b3a2a2f2d4bf09d7b6d455f17bed92021-11-17T06:43:50ZCollagen 1a1 Expression by Airway Macrophages Increases In Fibrotic ILDs and Is Associated With FVC Decline and Increased Mortality1664-322410.3389/fimmu.2021.645548https://doaj.org/article/db8b3a2a2f2d4bf09d7b6d455f17bed92021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.645548/fullhttps://doaj.org/toc/1664-3224Within the Interstitial Lung Diseases (ILD), patients with idiopathic pulmonary fibrosis (IPF) and a subset of those with non-IPF fibrotic ILD have a distinct clinical phenotype of progression despite management. This group of patients has been collectively termed the progressive fibrotic phenotype (PFP). Their early recognition may facilitate access to antifibrotic therapies to prevent or slow progression. Macrophages/monocytes within the lung orchestrate the progression and maintenance of fibrosis. A novel role for monocyte-derived macrophages during tissue damage and wound healing is the expression of collagens. We examined Collagen 1a1 expression in airway macrophages from ILD patients at diagnosis. COL1A1 mRNA levels from BAL cells were elevated in IPF and Non-IPF patients. The presence of a UIP pattern and a subsequent progressive phenotype were significantly associated with the higher BAL COL1A1 levels. In Non-IPF patients, higher COL1A1 levels were associated with a more than twofold increase in mortality. The intracellular localisation of COL1A1 in airway macrophages was demonstrated by confocal microscopy in CD45 and CD163 co-staining assays. Additionally, airway macrophages co-expressed COL1A1 with the profibrotic SPP1 gene product osteopontin. The levels of SPP1 mRNA and OPN in the BAL were significantly higher in IPF and Non-IPF patients relative to healthy. Our results suggest that profibrotic airway macrophages are increased in the BAL of patients with IPF and other ILDs and co-express COL1A1 and OPN. Importantly, COL1A1 expression by pro-fibrotic airway macrophages could be a marker of disease progression and poor survival in ILDs.Eliza TsitouraAthina TrachalakiAthina TrachalakiEirini VasarmidiSemeli MastrodemouGeorge A. MargaritopoulosMaria KokosiDionysios FanidisApostolos GalarisVassilis AidinisElizabeth RenzoniNikos TzanakisAthol U. WellsKaterina M. AntoniouFrontiers Media S.A.articleIPFRA-ILDNSIPairway macrophagesSPP1osteopontinImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	IPF RA-ILD NSIP airway macrophages SPP1 osteopontin Immunologic diseases. Allergy RC581-607
spellingShingle	IPF RA-ILD NSIP airway macrophages SPP1 osteopontin Immunologic diseases. Allergy RC581-607 Eliza Tsitoura Athina Trachalaki Athina Trachalaki Eirini Vasarmidi Semeli Mastrodemou George A. Margaritopoulos Maria Kokosi Dionysios Fanidis Apostolos Galaris Vassilis Aidinis Elizabeth Renzoni Nikos Tzanakis Athol U. Wells Katerina M. Antoniou Collagen 1a1 Expression by Airway Macrophages Increases In Fibrotic ILDs and Is Associated With FVC Decline and Increased Mortality
description	Within the Interstitial Lung Diseases (ILD), patients with idiopathic pulmonary fibrosis (IPF) and a subset of those with non-IPF fibrotic ILD have a distinct clinical phenotype of progression despite management. This group of patients has been collectively termed the progressive fibrotic phenotype (PFP). Their early recognition may facilitate access to antifibrotic therapies to prevent or slow progression. Macrophages/monocytes within the lung orchestrate the progression and maintenance of fibrosis. A novel role for monocyte-derived macrophages during tissue damage and wound healing is the expression of collagens. We examined Collagen 1a1 expression in airway macrophages from ILD patients at diagnosis. COL1A1 mRNA levels from BAL cells were elevated in IPF and Non-IPF patients. The presence of a UIP pattern and a subsequent progressive phenotype were significantly associated with the higher BAL COL1A1 levels. In Non-IPF patients, higher COL1A1 levels were associated with a more than twofold increase in mortality. The intracellular localisation of COL1A1 in airway macrophages was demonstrated by confocal microscopy in CD45 and CD163 co-staining assays. Additionally, airway macrophages co-expressed COL1A1 with the profibrotic SPP1 gene product osteopontin. The levels of SPP1 mRNA and OPN in the BAL were significantly higher in IPF and Non-IPF patients relative to healthy. Our results suggest that profibrotic airway macrophages are increased in the BAL of patients with IPF and other ILDs and co-express COL1A1 and OPN. Importantly, COL1A1 expression by pro-fibrotic airway macrophages could be a marker of disease progression and poor survival in ILDs.
format	article
author	Eliza Tsitoura Athina Trachalaki Athina Trachalaki Eirini Vasarmidi Semeli Mastrodemou George A. Margaritopoulos Maria Kokosi Dionysios Fanidis Apostolos Galaris Vassilis Aidinis Elizabeth Renzoni Nikos Tzanakis Athol U. Wells Katerina M. Antoniou
author_facet	Eliza Tsitoura Athina Trachalaki Athina Trachalaki Eirini Vasarmidi Semeli Mastrodemou George A. Margaritopoulos Maria Kokosi Dionysios Fanidis Apostolos Galaris Vassilis Aidinis Elizabeth Renzoni Nikos Tzanakis Athol U. Wells Katerina M. Antoniou
author_sort	Eliza Tsitoura
title	Collagen 1a1 Expression by Airway Macrophages Increases In Fibrotic ILDs and Is Associated With FVC Decline and Increased Mortality
title_short	Collagen 1a1 Expression by Airway Macrophages Increases In Fibrotic ILDs and Is Associated With FVC Decline and Increased Mortality
title_full	Collagen 1a1 Expression by Airway Macrophages Increases In Fibrotic ILDs and Is Associated With FVC Decline and Increased Mortality
title_fullStr	Collagen 1a1 Expression by Airway Macrophages Increases In Fibrotic ILDs and Is Associated With FVC Decline and Increased Mortality
title_full_unstemmed	Collagen 1a1 Expression by Airway Macrophages Increases In Fibrotic ILDs and Is Associated With FVC Decline and Increased Mortality
title_sort	collagen 1a1 expression by airway macrophages increases in fibrotic ilds and is associated with fvc decline and increased mortality
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/db8b3a2a2f2d4bf09d7b6d455f17bed9
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Collagen 1a1 Expression by Airway Macrophages Increases In Fibrotic ILDs and Is Associated With FVC Decline and Increased Mortality

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