title: Colony-stimulating factor-1 signaling suppresses renal crystal formation.
abstract: We recently reported evidence suggesting that migrating macrophages (Mϕs) eliminate renal crystals in hyperoxaluric mice. Mϕs can be inflammatory (M1) or anti-inflammatory (M2), and colony-stimulating factor-1 (CSF-1) mediates polarization to the M2Mϕ phenotype. M2Mϕs promote renal tissue repair and regeneration, but it is not clear whether these cells are involved in suppressing renal crystal formation. We investigated the role of M2Mϕs in renal crystal formation during hyperoxaluria using CSF-1-deficient mice, which lack M2Mϕs. Compared with wild-type mice, CSF-1-deficient mice had significantly higher amounts of renal calcium oxalate crystal deposition. Treatment with recombinant human CSF-1 increased the expression of M2-related genes and markedly decreased the number of renal crystals in both CSF-1-deficient and wild-type mice. Flow cytometry of sorted renal Mϕs showed that CSF-1 deficiency resulted in a smaller population of CD11b(+)F4/80(+)CD163(+)CD206(hi) cells, which represent M2-like Mϕs. Additionally, transfusion of M2Mϕs into CSF-1-deficient mice suppressed renal crystal deposition. In vitro phagocytosis assays with calcium oxalate monohydrate crystals showed a higher rate of crystal phagocytosis by M2-polarized Mϕs than M1-polarized Mϕs or renal tubular cells. Gene array profiling showed that CSF-1 deficiency resulted in disordered M2- and stone-related gene expressions. Collectively, our results provide compelling evidence for a suppressive role of CSF-1 signaling in renal crystal formation.
authors.affiliation: Departments of Nephro-urology, and.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Departments of Nephro-urology, and a-okada@med.nagoya-cu.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okada
authors.affiliation: Comparative and Experimental Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; and.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kitamura
authors.affiliation: Departments of Nephro-urology, and.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yasui
authors.affiliation: Departments of Nephro-urology, and.
authors.forename: Taku
authors.initials: T
authors.lastname: Naiki
authors.affiliation: Departments of Nephro-urology, and.
authors.forename: Shuzo
authors.initials: S
authors.lastname: Hamamoto
authors.affiliation: Departments of Nephro-urology, and.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Ando
authors.affiliation: Departments of Nephro-urology, and.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Mizuno
authors.affiliation: Departments of Nephro-urology, and.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Kawai
authors.affiliation: Departments of Nephro-urology, and.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tozawa
authors.affiliation: Laboratory of Immune Regulation, School of Science, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Asano
authors.affiliation: Laboratory of Immune Regulation, School of Science, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Comparative and Experimental Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; and.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Miyoshi
authors.affiliation: Departments of Nephro-urology, and.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kohri
mesh_terms: D000818:Animals; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D002129:Calcium Oxalate / Q000378:metabolism; D018929:Cell Culture Techniques; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D006959:Hyperoxaluria / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D007669:Kidney Calculi / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D017306:Annexin A2; D000943:Antigens, Differentiation; D018932:Chemokine CCL2; D018960:Hyaluronan Receptors; D012333:RNA, Messenger; D011994:Recombinant Proteins; C036763:monocyte-macrophage differentiation antigen; D053495:Osteopontin; D002129:Calcium Oxalate; D016173:Macrophage Colony-Stimulating Factor