Fetuin-A-containing calciprotein particles reduce mineral stress in the macrophage.

The formation of fetuin-A-containing calciprotein particles (CPP) may facilitate the clearance of calcium phosphate nanocrystals from the extracellular fluid. These crystals may otherwise seed extra-osseous mineralization. Fetuin-A is a partially phosphorylated glycoprotein that plays a critical rol...

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Autores principales:	Edward R Smith, Eric Hanssen, Lawrence P McMahon, Stephen G Holt
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e2f721cc191b4fd490355b82d6890c22
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spelling	oai:doaj.org-article:e2f721cc191b4fd490355b82d6890c222021-11-18T07:50:19ZFetuin-A-containing calciprotein particles reduce mineral stress in the macrophage.1932-620310.1371/journal.pone.0060904https://doaj.org/article/e2f721cc191b4fd490355b82d6890c222013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23577176/?tool=EBIhttps://doaj.org/toc/1932-6203The formation of fetuin-A-containing calciprotein particles (CPP) may facilitate the clearance of calcium phosphate nanocrystals from the extracellular fluid. These crystals may otherwise seed extra-osseous mineralization. Fetuin-A is a partially phosphorylated glycoprotein that plays a critical role in stabilizing these particles, inhibiting crystal growth and aggregation. CPP removal is thought to be predominantly mediated by cells of the reticuloendothelial system via type I and type II class A scavenger receptor (SR-AI/II). Naked calcium phosphate crystals are known to stimulate macrophages and other cell types in vitro, but little is known of the effect of CPP on these cells. We report here, for the first time, that CPP induce expression and secretion of tumour necrosis factor (TNF)-α, interleukin (IL)-1β in murine RAW 264.7 macrophages. Importantly, however, CPP induced significantly lower cytokine secretion than hydroxyapatite (HAP) crystals of equivalent size and calcium content. Furthermore, CPP only had a modest effect on macrophage viability and apoptosis, even at very high levels, compared to HAP crystals, which were strongly pro-apoptotic at much lower levels. Fetuin-A phosphorylation was found to modulate the effect of CPP on cytokine secretion and apoptosis, but not uptake via SR-AI/II. Prolonged exposure of macrophages to CPP was found to result in up-regulated expression of SR-AI/II. CPP formation may help protect against some of the pro-inflammatory and harmful effects of calcium phosphate nanocrystals, perhaps representing a natural defense system for calcium mineral stress. However, in pathological states where production exceeds clearance capacity, these particles may still stimulate pro-inflammatory and pro-apoptotic cascades in macrophages, which may be important in the pathogenesis of vascular calcification.Edward R SmithEric HanssenLawrence P McMahonStephen G HoltStephen G HoltPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e60904 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Edward R Smith Eric Hanssen Lawrence P McMahon Stephen G Holt Stephen G Holt Fetuin-A-containing calciprotein particles reduce mineral stress in the macrophage.
description	The formation of fetuin-A-containing calciprotein particles (CPP) may facilitate the clearance of calcium phosphate nanocrystals from the extracellular fluid. These crystals may otherwise seed extra-osseous mineralization. Fetuin-A is a partially phosphorylated glycoprotein that plays a critical role in stabilizing these particles, inhibiting crystal growth and aggregation. CPP removal is thought to be predominantly mediated by cells of the reticuloendothelial system via type I and type II class A scavenger receptor (SR-AI/II). Naked calcium phosphate crystals are known to stimulate macrophages and other cell types in vitro, but little is known of the effect of CPP on these cells. We report here, for the first time, that CPP induce expression and secretion of tumour necrosis factor (TNF)-α, interleukin (IL)-1β in murine RAW 264.7 macrophages. Importantly, however, CPP induced significantly lower cytokine secretion than hydroxyapatite (HAP) crystals of equivalent size and calcium content. Furthermore, CPP only had a modest effect on macrophage viability and apoptosis, even at very high levels, compared to HAP crystals, which were strongly pro-apoptotic at much lower levels. Fetuin-A phosphorylation was found to modulate the effect of CPP on cytokine secretion and apoptosis, but not uptake via SR-AI/II. Prolonged exposure of macrophages to CPP was found to result in up-regulated expression of SR-AI/II. CPP formation may help protect against some of the pro-inflammatory and harmful effects of calcium phosphate nanocrystals, perhaps representing a natural defense system for calcium mineral stress. However, in pathological states where production exceeds clearance capacity, these particles may still stimulate pro-inflammatory and pro-apoptotic cascades in macrophages, which may be important in the pathogenesis of vascular calcification.
format	article
author	Edward R Smith Eric Hanssen Lawrence P McMahon Stephen G Holt Stephen G Holt
author_facet	Edward R Smith Eric Hanssen Lawrence P McMahon Stephen G Holt Stephen G Holt
author_sort	Edward R Smith
title	Fetuin-A-containing calciprotein particles reduce mineral stress in the macrophage.
title_short	Fetuin-A-containing calciprotein particles reduce mineral stress in the macrophage.
title_full	Fetuin-A-containing calciprotein particles reduce mineral stress in the macrophage.
title_fullStr	Fetuin-A-containing calciprotein particles reduce mineral stress in the macrophage.
title_full_unstemmed	Fetuin-A-containing calciprotein particles reduce mineral stress in the macrophage.
title_sort	fetuin-a-containing calciprotein particles reduce mineral stress in the macrophage.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/e2f721cc191b4fd490355b82d6890c22
work_keys_str_mv	AT edwardrsmith fetuinacontainingcalciproteinparticlesreducemineralstressinthemacrophage AT erichanssen fetuinacontainingcalciproteinparticlesreducemineralstressinthemacrophage AT lawrencepmcmahon fetuinacontainingcalciproteinparticlesreducemineralstressinthemacrophage AT stephengholt fetuinacontainingcalciproteinparticlesreducemineralstressinthemacrophage AT stephengholt fetuinacontainingcalciproteinparticlesreducemineralstressinthemacrophage
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Fetuin-A-containing calciprotein particles reduce mineral stress in the macrophage.

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