title: M1/M2-macrophage phenotypes regulate renal calcium oxalate crystal development.
abstract: In our previous report, M2-macrophage (Mφs) deficient mice showed increased renal calcium oxalate (CaOx) crystal formation; however, the role of Mφs-related-cytokines and chemokines that affect kidney stone formation remains unknown. Here, we investigated the role of M1/M2s in crystal development by using in vitro and in vivo approaches. The crystal phagocytic rate of bone marrow-derived M2Mφs was higher than that of bone marrow-derived Mφs and M1Mφs and increased on co-culture with renal tubular cells (RTCs). However, the amount of crystal attachment on RTCs reduced on co-culture with M2Mφs. In six hyperoxaluric C57BL/6J mice, M1Mφ transfusion and induction by LPS and IFN-γ facilitated renal crystal formation, whereas M2Mφ transfusion and induction by IL-4 and IL-13 suppressed renal crystal formation compared with the control. These M2Mφ treatments reduced the expression of crystal-related genes, such as osteopontin and CD44, whereas M1Mφ treatment increased the expression of pro-inflammatory and adhesion-related genes such as IL-6, inducible NOS, TNF-α, C3, and VCAM-1. The expression of M2Mφ-related genes was lower whereas that of M1Mφ-related genes was higher in papillary tissue of CaOx stone formers. Overall, our results suggest that renal crystal development is facilitated by M1Mφs, but suppressed by M2Mφs.
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okada
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Shuzo
authors.initials: S
authors.lastname: Hamamoto
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Unno
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Moritoki
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Ando
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Mizuno
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Tozawa
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kohri
authors.affiliation: Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yasui
mesh_terms: D000818:Animals; D002129:Calcium Oxalate / Q000378:metabolism* / Q000652:urine; D002448:Cell Adhesion / Q000235:genetics; D018932:Chemokine CCL2 / Q000235:genetics; D018920:Coculture Techniques; D003460:Crystallization; D015870:Gene Expression; D018960:Hyaluronan Receptors / Q000235:genetics; D006959:Hyperoxaluria / Q000150:complications / Q000378:metabolism; D007669:Kidney Calculi / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000145:classification / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053495:Osteopontin / Q000235:genetics; D010641:Phenotype
chemical_list: C491768:Ccl2 protein, mouse; C476399:Cd44 protein, mouse; D018932:Chemokine CCL2; D018960:Hyaluronan Receptors; C506896:Spp1 protein, mouse; D053495:Osteopontin; D002129:Calcium Oxalate