Clearance of Fetuin-A–Containing Calciprotein Particles Is Mediated by Scavenger Receptor-A

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 fac...