MP25-12 HUMAN MACROPHAGES FACILITATE KIDNEY STONE CLEARANCES

You have accessJournal of UrologyStone Disease: Basic Research II1 Apr 2014MP25-12 HUMAN MACROPHAGES FACILITATE KIDNEY STONE CLEARANCES Sergei Kusmartsev, Paul Dominguez Gutierrez, Benjamin Canales, Johannes Vieweg, and Saeed Khan Sergei KusmartsevSergei Kusmartsev More articles by this author , Paul Dominguez GutierrezPaul Dominguez Gutierrez More articles by this author , Benjamin CanalesBenjamin Canales More articles by this author , Johannes ViewegJohannes Vieweg More articles by this author , and Saeed KhanSaeed Khan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.314AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Kidney stones affect one of eleven Americans, costing 10 billion dollars yearly to treat. Renal macrophages play a critical role to maintain healthy, functional kidneys. In this report, we investigate macrophage phagocytic and inflammatory responses to natural stones as well as to inorganic crystals- calcium oxalate (CaOx) and calcium phosphate (CaP) crystals. METHODS Human buffy coats were purchased from Life South Community Blood Center. The peripheral blood mononuclear cells were collected by histopaque-1077 and monocytes were purified using CD14 Miltenyi Biotec magnetic microbeads. Monocytes were differentiated into macrophages with macrophage colony-stimulating factor over a 7-day period. Macrophages were treated with crushed natural stones from human donors and synthetically produced CaOx and CaP crystals. Untreated macrophages were used as controls. Macrophage phagocytosis and morphological changes were observed in x200 and x400 field with a light microscope. Thirty-one Chemokine and thirty-six Cytokine protein levels in the cell supernatant were measured with R&D Proteome Profiler Human Array kits at 24 hours. RESULTS Within 24 hours, natural stones and both crystal types were surrounded by macrophages (A, B). Between 24 and 48 hours, small stones/crystals were visibly being phagocytized by the macrophages leading to their gradual destruction (C, arrows) while larger stones/crystals were more resistant to the macrophage-mediated destruction. Macrophages that phagocytized stones/crystals displayed dark spots, indicative of mineral uptake (D). CCL2, CCL22, and MIP-1α/β were upregulated in macrophages exposed to all three stone types. Natural stone and CaOx crystals increased C5/C5a, IL-1ra, and IL-8 within supernatant, but these signaling proteins were decreased in response to CaP crystals compared to controls. CONCLUSIONS Human macrophages are capable of phagocytizing and eroding naturally-produced kidney stones. Composition of the stone appears to play a role in chemokine and cytokine production. The present study suggests that macrophages play an important role in clearing stones and initiating an immune response. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e271 Advertisement Copyright & Permissions© 2014Metrics Author Information Sergei Kusmartsev More articles by this author Paul Dominguez Gutierrez More articles by this author Benjamin Canales More articles by this author Johannes Vieweg More articles by this author Saeed Khan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...