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Novel phosphate-activated macrophages prevent ectopic calcification by increasing extracellular ATP and pyrophosphate

PURPOSE: Phosphorus is an essential nutrient involved in many pathobiological processes. Less than 1% of phosphorus is found in extracellular fluids as inorganic phosphate ion (Pi) in solution. High serum Pi level promotes ectopic calcification in many tissues, including blood vessels. Here, we stud...

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Detalles Bibliográficos
Autores principales: Villa-Bellosta, Ricardo, Hamczyk, Magda R., Andrés, Vicente
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376322/
https://www.ncbi.nlm.nih.gov/pubmed/28362852
http://dx.doi.org/10.1371/journal.pone.0174998
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author Villa-Bellosta, Ricardo
Hamczyk, Magda R.
Andrés, Vicente
author_facet Villa-Bellosta, Ricardo
Hamczyk, Magda R.
Andrés, Vicente
author_sort Villa-Bellosta, Ricardo
collection PubMed
description PURPOSE: Phosphorus is an essential nutrient involved in many pathobiological processes. Less than 1% of phosphorus is found in extracellular fluids as inorganic phosphate ion (Pi) in solution. High serum Pi level promotes ectopic calcification in many tissues, including blood vessels. Here, we studied the effect of elevated Pi concentration on macrophage polarization and calcification. Macrophages, present in virtually all tissues, play key roles in health and disease and display remarkable plasticity, being able to change their physiology in response to environmental cues. METHODS AND RESULTS: High-throughput transcriptomic analysis and functional studies demonstrated that Pi induces unpolarized macrophages to adopt a phenotype closely resembling that of alternatively-activated M2 macrophages, as revealed by arginine hydrolysis and energetic and antioxidant profiles. Pi-induced macrophages showed an anti-calcifying action mediated by increased availability of extracellular ATP and pyrophosphate. CONCLUSION: We conclude that the ability of Pi-activated macrophages to prevent calcium-phosphate deposition is a compensatory mechanism protecting tissues from hyperphosphatemia-induced pathologic calcification.
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spelling pubmed-53763222017-04-07 Novel phosphate-activated macrophages prevent ectopic calcification by increasing extracellular ATP and pyrophosphate Villa-Bellosta, Ricardo Hamczyk, Magda R. Andrés, Vicente PLoS One Research Article PURPOSE: Phosphorus is an essential nutrient involved in many pathobiological processes. Less than 1% of phosphorus is found in extracellular fluids as inorganic phosphate ion (Pi) in solution. High serum Pi level promotes ectopic calcification in many tissues, including blood vessels. Here, we studied the effect of elevated Pi concentration on macrophage polarization and calcification. Macrophages, present in virtually all tissues, play key roles in health and disease and display remarkable plasticity, being able to change their physiology in response to environmental cues. METHODS AND RESULTS: High-throughput transcriptomic analysis and functional studies demonstrated that Pi induces unpolarized macrophages to adopt a phenotype closely resembling that of alternatively-activated M2 macrophages, as revealed by arginine hydrolysis and energetic and antioxidant profiles. Pi-induced macrophages showed an anti-calcifying action mediated by increased availability of extracellular ATP and pyrophosphate. CONCLUSION: We conclude that the ability of Pi-activated macrophages to prevent calcium-phosphate deposition is a compensatory mechanism protecting tissues from hyperphosphatemia-induced pathologic calcification. Public Library of Science 2017-03-31 /pmc/articles/PMC5376322/ /pubmed/28362852 http://dx.doi.org/10.1371/journal.pone.0174998 Text en © 2017 Villa-Bellosta et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Villa-Bellosta, Ricardo
Hamczyk, Magda R.
Andrés, Vicente
Novel phosphate-activated macrophages prevent ectopic calcification by increasing extracellular ATP and pyrophosphate
title Novel phosphate-activated macrophages prevent ectopic calcification by increasing extracellular ATP and pyrophosphate
title_full Novel phosphate-activated macrophages prevent ectopic calcification by increasing extracellular ATP and pyrophosphate
title_fullStr Novel phosphate-activated macrophages prevent ectopic calcification by increasing extracellular ATP and pyrophosphate
title_full_unstemmed Novel phosphate-activated macrophages prevent ectopic calcification by increasing extracellular ATP and pyrophosphate
title_short Novel phosphate-activated macrophages prevent ectopic calcification by increasing extracellular ATP and pyrophosphate
title_sort novel phosphate-activated macrophages prevent ectopic calcification by increasing extracellular atp and pyrophosphate
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376322/
https://www.ncbi.nlm.nih.gov/pubmed/28362852
http://dx.doi.org/10.1371/journal.pone.0174998
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