MP58-09 HYDROXYAPATITE INDUCES CALCIUM OXALATE TOLERANCE IN PRIMARY HUMAN MONOCYTES

Abstract

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology I1 Apr 2016MP58-09 HYDROXYAPATITE INDUCES CALCIUM OXALATE TOLERANCE IN PRIMARY HUMAN MONOCYTES Paul Dominguez Gutierrez, Sergei Kusmartsev, Benjamin Canales, Vincent Bird, Johannes Vieweg, and Saeed Khan Paul Dominguez GutierrezPaul Dominguez Gutierrez More articles by this author , Sergei KusmartsevSergei Kusmartsev More articles by this author , Benjamin CanalesBenjamin Canales More articles by this author , Vincent BirdVincent Bird 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.2016.02.807AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Although most crystal deposits within tissue produce inflammation, renal interstitial hydroxyapatite deposits most like do not, accumulating as Randall's plaque. To further explore this lack of response, we investigated the effect of oxalate, hydroxyapatite (HA), and combination of both on time dependent, immunological responses in human monocytes, the precursors to tissue macrophages. METHODS Primary human monocytes and human monocytic cell line THP-1 cells were exposed to varying concentrations of soluble potassium oxalate (KOx) or insoluble CaOx and HA crystals. Primary human monocytes cells were pre-treated with 100 ug/ml of HA or CaOx followed by secondary treatment with 100 ug/ml HA, 100 ug/ml CaOx, and 1 ug/ml LPS. Cells were collected at various times after various treatments, and RNA was analyzed by quantitative real time PCR. Furthermore, monocytes function to enhance macrophage function and differentiation in the presence of CaOx where observed. RESULTS Primary monocytes and THP-1 cells responded strongly to CaOx in a dose dependent manner producing TNFa, IL-1b, IL-8, and IL-10 with little to no response to KOx and HA. Pre-exposure to HA had little effect on human monocytes response to CaOx and LPS exposure; however, pre-exposure to CaOx followed by HA negated cytokine production. CONCLUSIONS CaOx stimulates monocytes to produce cytokines and chemokines which function to stimulate and enhance macrophage uptake of CaOx; furthermore, monocytes exposed to CaOx go on to differentiate into macrophages. Furthermore, CaOx recognition by monocytes appears to be specific. Monocytes exposed to CaOx followed by LPS produce more cytokiens than LPS; however, monocytes exposed to LPS followed CaOx display a greatly downregulate response compared to LPS alone. HA, a component of Randal’s plaques, does not stimulate monocytes; however, it functions to specifically downregulate monocyte response to CaOx while having no effect upon LPS exposed monocytes. This tolerance mechanism may partially explain the lack of papillary inflammation in the pathogenesis of Randall's plaque. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e779 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Paul Dominguez Gutierrez More articles by this author Sergei Kusmartsev More articles by this author Benjamin Canales More articles by this author Vincent Bird 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 ...