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- W32137290 abstract "Abstract Macrophages (M(s) play decisive roles in different models of organ fibrosis. Prevailing concepts support circulating monocyte heterogeneity, subpopulation discrete recruitment into injured tissues, differentiation into M(s, and possibly subpopulation discrete roles in injury and repair. Here we show discrete subpopulations of M(s in fibrotic kidney induced by unilateral ureteral obstruction (UUO) and their discrete functional roles in renal fibrosis. Fluorescence-activated cell sorting (FACS) of purified UUO kidney leukocytes reveals 3 populations of M(s separated by Ly6C: high, intermediate, and low. FACS of peripheral blood mononuclear cells (PBMC) showed a marked increase in Ly6chi-Mo in response to kidney injury. Depletion of M(s in CD11b-DTR mice during UUO fibrosis inhibits the progression of fibrosis by an indirect mechanism. However, Ly6clo kidney M(s were selectively depleted indicating their predominant role in fibrogenesis. To determine the origins of kidney M(s, we lineage-traced 3 different populations of monocytes (Mo) by adoptive transfer of CD45.1+ bone marrow (BM)-Ly6chi Mo or peripheral blood (PB) Ly6chi Mo or PB-Ly6clo-Mo into CD45.2 mice with UUO. Ly6Chi BM-Mo were avidly recruited to injured kidney, and differentiated into Ly6Chi, Ly6Cint, and Ly6Clo kidney M(s. PB-Mo also differentiated into 3 populations but 20-fold lower recruitment was observed. We characterized kidney-M(-subpopulation transcript levels by branched-chain-DNA-technology which demonstrated discrete differences in expression of genes including TNF(, IL1(, MIP2, MIP1(. We conclude that Ly6Chi BM-Mo are recruited to kidney by mobilization from BM, differentiate into 3 functionally discrete kidney M(s one of which is profibrotic, and resident M(s play a non-fibrogenic role in kidney injury." @default.
- W32137290 created "2016-06-24" @default.
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- W32137290 date "2009-04-01" @default.
- W32137290 modified "2023-09-26" @default.
- W32137290 title "Bone marrow Ly6Chi Monocytes are recruited to injured kidney and differentiate into Ly6Clo profibrotic macrophages (92.7)" @default.
- W32137290 doi "https://doi.org/10.4049/jimmunol.182.supp.92.7" @default.
- W32137290 hasPublicationYear "2009" @default.
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