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The Elusive Antifibrotic Macrophage

Fibrotic diseases, especially of the liver, the cardiovascular system, the kidneys, and the lungs, account for approximately 45% of deaths in Western societies. Fibrosis is a serious complication associated with aging and/or chronic inflammation or injury and cannot be treated effectively yet. It is...

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Autores principales: Adhyatmika, Adhyatmika, Putri, Kurnia S. S., Beljaars, Leonie, Melgert, Barbro N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643133/
https://www.ncbi.nlm.nih.gov/pubmed/26618160
http://dx.doi.org/10.3389/fmed.2015.00081
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author Adhyatmika, Adhyatmika
Putri, Kurnia S. S.
Beljaars, Leonie
Melgert, Barbro N.
author_facet Adhyatmika, Adhyatmika
Putri, Kurnia S. S.
Beljaars, Leonie
Melgert, Barbro N.
author_sort Adhyatmika, Adhyatmika
collection PubMed
description Fibrotic diseases, especially of the liver, the cardiovascular system, the kidneys, and the lungs, account for approximately 45% of deaths in Western societies. Fibrosis is a serious complication associated with aging and/or chronic inflammation or injury and cannot be treated effectively yet. It is characterized by excessive deposition of extracellular matrix (ECM) proteins by myofibroblasts and impaired degradation by macrophages. This ultimately destroys the normal structure of an organ, which leads to loss of function. Most efforts to develop drugs have focused on inhibiting ECM production by myofibroblasts and have not yielded many effective drugs yet. Another option is to stimulate the cells that are responsible for degradation and uptake of excess ECM, i.e., antifibrotic macrophages. However, macrophages are plastic cells that have many faces in fibrosis, including profibrotic behavior-stimulating ECM production. This can be dependent on their origin, as the different organs have tissue-resident macrophages with different origins and a various influx of incoming monocytes in steady-state conditions and during fibrosis. To be able to pharmacologically stimulate the right kind of behavior in fibrosis, a thorough characterization of antifibrotic macrophages is necessary, as well as an understanding of the signals they need to degrade ECM. In this review, we will summarize the current state of the art regarding the antifibrotic macrophage phenotype and the signals that stimulate its behavior.
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spelling pubmed-46431332015-11-27 The Elusive Antifibrotic Macrophage Adhyatmika, Adhyatmika Putri, Kurnia S. S. Beljaars, Leonie Melgert, Barbro N. Front Med (Lausanne) Medicine Fibrotic diseases, especially of the liver, the cardiovascular system, the kidneys, and the lungs, account for approximately 45% of deaths in Western societies. Fibrosis is a serious complication associated with aging and/or chronic inflammation or injury and cannot be treated effectively yet. It is characterized by excessive deposition of extracellular matrix (ECM) proteins by myofibroblasts and impaired degradation by macrophages. This ultimately destroys the normal structure of an organ, which leads to loss of function. Most efforts to develop drugs have focused on inhibiting ECM production by myofibroblasts and have not yielded many effective drugs yet. Another option is to stimulate the cells that are responsible for degradation and uptake of excess ECM, i.e., antifibrotic macrophages. However, macrophages are plastic cells that have many faces in fibrosis, including profibrotic behavior-stimulating ECM production. This can be dependent on their origin, as the different organs have tissue-resident macrophages with different origins and a various influx of incoming monocytes in steady-state conditions and during fibrosis. To be able to pharmacologically stimulate the right kind of behavior in fibrosis, a thorough characterization of antifibrotic macrophages is necessary, as well as an understanding of the signals they need to degrade ECM. In this review, we will summarize the current state of the art regarding the antifibrotic macrophage phenotype and the signals that stimulate its behavior. Frontiers Media S.A. 2015-11-13 /pmc/articles/PMC4643133/ /pubmed/26618160 http://dx.doi.org/10.3389/fmed.2015.00081 Text en Copyright © 2015 Adhyatmika, Putri, Beljaars and Melgert. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Medicine
Adhyatmika, Adhyatmika
Putri, Kurnia S. S.
Beljaars, Leonie
Melgert, Barbro N.
The Elusive Antifibrotic Macrophage
title The Elusive Antifibrotic Macrophage
title_full The Elusive Antifibrotic Macrophage
title_fullStr The Elusive Antifibrotic Macrophage
title_full_unstemmed The Elusive Antifibrotic Macrophage
title_short The Elusive Antifibrotic Macrophage
title_sort elusive antifibrotic macrophage
topic Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4643133/
https://www.ncbi.nlm.nih.gov/pubmed/26618160
http://dx.doi.org/10.3389/fmed.2015.00081
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