title: Clearance of fetuin-A--containing calciprotein particles is mediated by scavenger receptor-A.
abstract: BACKGROUND
  Fetuin-A is a liver-derived plasma protein involved in the regulation of calcified matrix metabolism. Biochemical studies showed that fetuin-A is essential for the formation of protein-mineral complexes, called calciprotein particles (CPPs). CPPs must be cleared from circulation to prevent local deposition and pathological calcification.
  
  
  OBJECTIVE
  We studied CPP clearance in mice and in cell culture to identify the tissues, cells, and receptors involved in the clearance.
  
  
  RESULTS
  In mice, fetuin-A-containing CPPs were rapidly cleared by the reticuloendothelial system, namely Kupffer cells of the liver and marginal zone macrophages of the spleen. Macrophages from scavenger receptor-AI/II (SR-A)-deficient mice cleared CPPs less efficiently than macrophages from wild-type mice, suggesting that SR-AI/II is involved in CPP binding and endocytosis. Accordingly, we found reduced clearance of CPPs in SR-A/MARCO-deficient mice.
  
  
  CONCLUSIONS
  We could demonstrate that fetuin-A-containing CPPs facilitate the clearance of mineral debris by macrophages via SR-A. Since the same receptor also contributes to the uptake of modified low-density lipoprotein particles in atherosclerosis, defective endocytosis of both types of particle may impinge on lipid as well as mineral debris clearance in calcifying atherosclerosis.
authors: Helmholtz Institute for Biomedical Engineering, Biointerface Group, RWTH Aachen University, Pauwelsstrasse 30, 52074 Aachen, Germany.
authors: Marietta
authors: M
authors: Herrmann
authors: Cora
authors: C
authors: Schäfer
authors: Alexander
authors: A
authors: Heiss
authors: Steffen
authors: S
authors: Gräber
authors: Anne
authors: A
authors: Kinkeldey
authors: Andrea
authors: A
authors: Büscher
authors: Martin M N
authors: MM
authors: Schmitt
authors: Jörg
authors: J
authors: Bornemann
authors: Falk
authors: F
authors: Nimmerjahn
authors: Martin
authors: M
authors: Herrmann
authors: Laura
authors: L
authors: Helming
authors: Siamon
authors: S
authors: Gordon
authors: Willi
authors: W
authors: Jahnen-Dechent
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D002113:Calcification, Physiologic / Q000502:physiology; D002114:Calcinosis / Q000378:metabolism / Q000473:pathology; D002118:Calcium / Q000097:blood*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002339:Carotid Arteries / Q000166:cytology; D002417:Cattle; D002460:Cell Line; D004705:Endocytosis / Q000502:physiology; D007728:Kupffer Cells / Q000166:cytology / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012157:Mononuclear Phagocyte System / Q000378:metabolism; D010710:Phosphates / Q000097:blood; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D051117:Scavenger Receptors, Class A / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology; D060749:alpha-2-HS-Glycoprotein / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
chemical_list: C556357:Ahsg protein, mouse; D001057:Apolipoproteins E; D002135:Calcium-Binding Proteins; D008077:Lipoproteins, LDL; C092228:Marco protein, mouse; D010710:Phosphates; D011971:Receptors, Immunologic; D051117:Scavenger Receptors, Class A; D060749:alpha-2-HS-Glycoprotein; D002118:Calcium