作者
Sergei A. Kusmartsev,Paul R. Dominguez‐Gutierrez,Benjamin K. Canales,Johannes Vieweg,Saeed Khan
摘要
You have accessJournal of UrologyStone Disease: Basic Research I1 Apr 2015MP33-09 HUMAN MONOCYTE-DERIVED MACROPHAGES ARE ABLE TO DESTROY KIDNEY STONES 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.2015.02.570AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Kidney stone disease nephrolithiasis caused by precipitating of inorganic material such as calcium oxalate and proteins on the surface of renal papillae. Resident and inflammatory macrophages play a critical role to maintain healthy, functional kidneys. As professional phagocytes/scavengers, macrophages perform critical functions in tissue maintenance and its remodeling. In this report, we investigate macrophage phagocytic and inflammatory responses to naturally-produced human kidney stones as well as to inorganic crystals-calcium oxalate (CaOx) and calcium phosphate (CaP) crystals. METHODS Kidney stones, size 3-5 mm, were obtained from patients undergoing kidney stone surgery after Institutional Review Board approval from University of Florida, Gainesville, FL. Stones were verified to be >95% calcium oxalate monohydrate using Fourier transform-infrared spectroscopy. Peripheral blood mononuclear cells from blood samples were separated by Lymphoprep. Monocytes were purified from PBMC using magnetic beads (Miltenyi Biotec). Monocytes were differentiated into macrophages using M-CSF or GM-CSF. Macrophage response to the natural kidney stones, or inorganic calcium oxalate (CaOx) and calcium phosphate (CaP) was assessed using Antibody Proteome Arrays (R&D Systems), RT PCR, fluorescent and light microscopy. RESULTS We demonstrate that human macrophages are capable of engulfment and eroding naturally-produced kidney stones as well as chemically synthesized crystals of CaOx and CaP. Macrophages surround stones/crystals and then step-by-step destroy small and medium-sized naturally produced kidney stones. Phagocytosis and clathrin-mediated endocytosis involved in this processes. Uptake of kidney stones or calcium crystalline particles by macrophages led to release of certain chemokines and cytokine production, including chemokines CCL2, CCL3, CCL22, interleukin-1 receptor antagonist (IL-1ra), complement component C5/C5a and IL-8. The response to stones/crystals depends on macrophage phenotype and activation status. Macrophage colony-stimulating factor appears to be important for formation and function of kidney stone-clearing macrophages. CONCLUSIONS Together, obtained results suggest that human mature macrophages could play an important role in preventing kidney stone disease by removing and digesting stones in kidney tissue. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e376-e377 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor 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 ...