title: Renal F4/80+ CD11c+ mononuclear phagocytes display phenotypic and functional characteristics of macrophages in health and in adriamycin nephropathy.
abstract: Conventional markers of macrophages (Mфs) and dendritic cells (DCs) lack specificity and often overlap, leading to confusion and controversy regarding the precise function of these cells in kidney and other diseases. This study aimed to identify the phenotype and function of renal mononuclear phagocytes (rMPs) expressing key markers of both Mфs and DCs. F4/80(+)CD11c(+) cells accounted for 45% of total rMPs in normal kidneys and in those from mice with Adriamycin nephropathy (AN). Despite expression of the DC marker CD11c, these double-positive rMPs displayed the features of Mфs, including Mф-like morphology, high expression of CD68, CD204, and CD206, and high phagocytic ability but low antigen-presenting ability. F4/80(+)CD11c(+) cells were found in the cortex but not in the medulla of the kidney. In AN, F4/80(+)CD11c(+) cells displayed an M1 Mф phenotype with high expression of inflammatory mediators and costimulatory factors. Adoptive transfer of F4/80(+)CD11c(+) cells separated from diseased kidney aggravated renal injury in AN mice. Furthermore, adoptive transfer of common progenitors revealed that kidney F4/80(+)CD11c(+) cells were derived predominantly from monocytes, but not from pre-DCs. In conclusion, renal F4/80(+)CD11c(+) cells are a major subset of rMPs and display Mф-like phenotypic and functional characteristics in health and in AN.
authors.affiliation: Centre for Transplant and Renal Research and qi.cao@sydney.edu.au.
authors.forename: Qi
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Centre for Transplant and Renal Research and.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Flow Cytometry Facility, Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia; and.
authors.forename: Xin Maggie
authors.initials: XM
authors.lastname: Wang
authors.affiliation: Centre for Transplant and Renal Research and.
authors.forename: Junyu
authors.initials: J
authors.lastname: Lu
authors.affiliation: Centre for Transplant and Renal Research and.
authors.forename: Vincent W S
authors.initials: VW
authors.lastname: Lee
authors.affiliation: Centre for Transplant and Renal Research and.
authors.forename: Qianling
authors.initials: Q
authors.lastname: Ye
authors.affiliation: Centre for Transplant and Renal Research and.
authors.forename: Hanh
authors.initials: H
authors.lastname: Nguyen
authors.affiliation: Centre for Transplant and Renal Research and.
authors.forename: Guoping
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Centre for Transplant and Renal Research and.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Centre for Kidney Research, Children's Hospital at Westmead, Sydney, New South Wales, Australia.
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Alexander
authors.affiliation: Centre for Transplant and Renal Research and.
authors.forename: David C H
authors.initials: DC
authors.lastname: Harris
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D018845:CD11 Antigens / Q000378:metabolism*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000009:adverse effects; D066298:In Vitro Techniques; D007668:Kidney / Q000473:pathology* / Q000502:physiology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D037181:Lectins, C-Type / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010586:Phagocytes / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000378:metabolism; D051117:Scavenger Receptors, Class A / Q000378:metabolism; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D018845:CD11 Antigens; D004317:Doxorubicin; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D051117:Scavenger Receptors, Class A; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C495140:Msr1 protein, mouse; C036763:monocyte-macrophage differentiation antigen
keywords: CKD; dendritic cells; macrophages; renal mononuclear phagocytes