Clearance of Fetuin-A–Containing Calciprotein Particles Is Mediated by Scavenger Receptor-A
| Autor: | Laura Helming, Alexander Heiss, Jörg Bornemann, Siamon Gordon, Martin Schmitt, Steffen Gräber, Marietta Herrmann, Cora Schäfer, Falk Nimmerjahn, Anne Kinkeldey, Andrea Büscher, Willi Jahnen-Dechent, Martin Herrmann |
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| Rok vydání: | 2012 |
| Předmět: |
Kupffer Cells
alpha-2-HS-Glycoprotein Physiology Spleen Biology Endocytosis Cell Line Phosphates Mice Apolipoproteins E Calcification Physiologic medicine Animals Receptors Immunologic Scavenger receptor Receptor Mononuclear Phagocyte System Mice Knockout Macrophages Calcium-Binding Proteins Calcinosis Scavenger Receptors Class A Mononuclear phagocyte system Atherosclerosis Fetuin Cell biology Lipoproteins LDL Mice Inbred C57BL Carotid Arteries medicine.anatomical_structure Biochemistry Cell culture Calcium Cattle Cardiology and Cardiovascular Medicine Lipoprotein |
| Zdroj: | Circulation Research. 111:575-584 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/circresaha.111.261479 |
| Popis: | Rationale: 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. Methods and 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. |
| Databáze: | OpenAIRE |
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