M1/M2-macrophage phenotypes regulate renal calcium oxalate crystal development.

ABSTRACT: In our previous report, M2-macrophage (M?s) deficient mice showed increased renal calcium oxalate (CaOx) crystal formation; however, the role of M?s-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 M2M?s was higher than that of bone marrow-derived M?s and M1M?s and increased on co-culture with renal tubular cells (RTCs). However, the amount of crystal attachment on RTCs reduced on co-culture with M2M?s. In six hyperoxaluric C57BL/6J mice, M1M? transfusion and induction by LPS and IFN-? facilitated renal crystal formation, whereas M2M? transfusion and induction by IL-4 and IL-13 suppressed renal crystal formation compared with the control. These M2M? treatments reduced the expression of crystal-related genes, such as osteopontin and CD44, whereas M1M? treatment increased the expression of pro-inflammatory and adhesion-related genes such as IL-6, inducible NOS, TNF-?, C3, and VCAM-1. The expression of M2M?-related genes was lower whereas that of M1M?-related genes was higher in papillary tissue of CaOx stone formers. Overall, our results suggest that renal crystal development is facilitated by M1M?s, but suppressed by M2M?s.

SUBMITTER: Taguchi K 

PROVIDER: S-EPMC5059697 | biostudies-other | 2016 Oct

REPOSITORIES: biostudies-other