title: Novel phosphate-activated macrophages prevent ectopic calcification by increasing extracellular ATP and pyrophosphate.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centro Nacional de Investigaciones CardiovascularesCarlos III (CNIC), Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.|Fundación Instituto de Investigación Sanitaria Fundación Jiménez Díaz (FIIS-FJD), Madrid, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Villa-Bellosta
authors.affiliation: Centro Nacional de Investigaciones CardiovascularesCarlos III (CNIC), Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
authors.forename: Magda R
authors.initials: MR
authors.lastname: Hamczyk
authors.affiliation: Centro Nacional de Investigaciones CardiovascularesCarlos III (CNIC), Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Andrés
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D011756:Diphosphates / Q000378:metabolism*; D005434:Flow Cytometry; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010710:Phosphates / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D061205:Vascular Calcification / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D011756:Diphosphates; D010710:Phosphates; C107241:diphosphoric acid; D000255:Adenosine Triphosphate; D002118:Calcium