You have accessJournal of UrologyStone Disease: Basic Research (I)1 Apr 20132084 ANTI-INFLAMMATORY M2 MACROPHAGES SUPPRESS RENAL CRYSTAL FORMATION VIA A COLONY STIMULATING FACTOR-1 DEPENDENT PATHWAY IN M2-DEFICIENT (OP/OP) MICE Kazumi Taguchi, Atsushi Okada, Takahiro Yasui, Kazuhiro Niimi, Yasuhiro Fujii, Shuzo Hamamoto, Masahito Hirose, Yukihiro Umemoto, Shoichi Sasaki, and Kenjiro Kohri Kazumi TaguchiKazumi Taguchi Nagoya, Japan More articles by this author , Atsushi OkadaAtsushi Okada Nagoya, Japan More articles by this author , Takahiro YasuiTakahiro Yasui Nagoya, Japan More articles by this author , Kazuhiro NiimiKazuhiro Niimi Nagoya, Japan More articles by this author , Yasuhiro FujiiYasuhiro Fujii Nagoya, Japan More articles by this author , Shuzo HamamotoShuzo Hamamoto Nagoya, Japan More articles by this author , Masahito HiroseMasahito Hirose Nagoya, Japan More articles by this author , Yukihiro UmemotoYukihiro Umemoto Nagoya, Japan More articles by this author , Shoichi SasakiShoichi Sasaki Nagoya, Japan More articles by this author , and Kenjiro KohriKenjiro Kohri Nagoya, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2503AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We have reported that an interesting phenomenon involving the spontaneous elimination of renal crystals using mice model and macrophages (Mϕ) were related to stone elimination as well as formation in a microarray study.(Okada et al. J Bone Miner Res. 2009) Mϕ show classically activated inflammatory (M1) or alternatively activated anti-inflammatory (M2) phenotypes. These findings suggested a correlation between the M2-macrophages and this crystal elimination to us. We investigated renal macrophage function in order to clarify their anti-inflammatory effect on stone formation using colony stimulating factor-1 (CSF-1)-deficient mice. METHODS We divided 8-week-old male CSF-1-deficient mice into 6 groups: wild type (+/+), heterozygous (+/op), homozygous (op/op), and each genotype injected with CSF-1 (+/+, +/op, op_CSF). They were administered 80 mg?kg−1 glyoxylate by daily intra-abdominal injection, and the kidneys were extracted to examine crystal formation at days 0 and 6. We performed iNOS, CD163, and CD206 staining to evaluate the expression of renal macrophages. iNOS was used for detection of M1-macrophages and double staining of CD163 and CD206 for M2. Morphological study of crystal formations were evaluated with scanning electron microscopy (SEM). Expression of genes for crystal-binding molecules was examined by immunohistochemistry (IHC) and quantitative reverse transcriptase polymerase chain reaction (qPCR). RESULTS Renal and urinary crystal amounts in op/op were markedly higher than those in +/+ and +/op, and CSF-1 supplementation dose-dependently decreased renal crystal formation in all groups (Figure). Crystal-binding molecule gene (e.g., osteopontin) expression levels were higher in op/op mice than in the other groups but were decreased by CSF-1 supplementation. The op/op mice showed M2 expression deficit and lower expression levels of M2-related genes (e.g., CD163), but M2 and M2-related gene expression were increased by CSF-1 supplementation. CONCLUSIONS Our study suggests that M2 reduces renal crystal formation and indicates that CSF-1 exhibits prophylactic activity against kidney stone formation by inducing M2. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e855 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kazumi Taguchi Nagoya, Japan More articles by this author Atsushi Okada Nagoya, Japan More articles by this author Takahiro Yasui Nagoya, Japan More articles by this author Kazuhiro Niimi Nagoya, Japan More articles by this author Yasuhiro Fujii Nagoya, Japan More articles by this author Shuzo Hamamoto Nagoya, Japan More articles by this author Masahito Hirose Nagoya, Japan More articles by this author Yukihiro Umemoto Nagoya, Japan More articles by this author Shoichi Sasaki Nagoya, Japan More articles by this author Kenjiro Kohri Nagoya, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...