title: CD163-Macrophages Are Involved in Rhabdomyolysis-Induced Kidney Injury and May Be Detected by MRI with Targeted Gold-Coated Iron Oxide Nanoparticles.
abstract: Macrophages play an important role in rhabdomyolysis-acute kidney injury (AKI), although the molecular mechanisms involved in macrophage differentiation are poorly understood. We analyzed the expression and regulation of CD163, a membrane receptor mainly expressed by anti-inflammatory M2 macrophages, in rhabdomyolysis-AKI and developed targeted probes for its specific detection in vivo by MRI. Intramuscular injection of glycerol in mice promoted an early inflammatory response, with elevated proportion of M1 macrophages, and partial differentiation towards a M2 phenotype in later stages, where increased CD163 expression was observed. Immunohistological studies confirmed the presence of CD163-macrophages in human rhabdomyolysis-AKI. In cultured macrophages, myoglobin upregulated CD163 expression via HO-1/IL-10 axis. Moreover, we developed gold-coated iron oxide nanoparticles vectorized with an anti-CD163 antibody that specifically targeted CD163 in kidneys from glycerol-injected mice, as determined by MRI studies, and confirmed by electron microscopy and immunological analysis. Our findings are the first to demonstrate that CD163 is present in both human and experimental rhabdomyolysis-induced AKI, suggesting an important role of this molecule in this pathological condition. Therefore, the use of probes targeting CD163-macrophages by MRI may provide important information about the cellular composition of renal lesion in rhabdomyolysis.
authors.affiliation: 1. Renal, Vascular and Diabetes Research Lab. Fundación Instituto de Investigaciones Sanitarias-Fundación Jiménez Díaz, Autónoma University. Av. Reyes Católicos 2, 28040, Madrid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Rubio-Navarro
authors.affiliation: 2. CIC biomaGUNE. Paseo Miramón, 182, 20009, San Sebastián, Spain.; 3. Ikerbasque, Basque Foundation for Science, 48011, Bilbao, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Carril
authors.affiliation: 2. CIC biomaGUNE. Paseo Miramón, 182, 20009, San Sebastián, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Padro
authors.affiliation: 1. Renal, Vascular and Diabetes Research Lab. Fundación Instituto de Investigaciones Sanitarias-Fundación Jiménez Díaz, Autónoma University. Av. Reyes Católicos 2, 28040, Madrid, Spain.
authors.forename: Melanie
authors.initials: M
authors.lastname: Guerrero-Hue
authors.affiliation: 1. Renal, Vascular and Diabetes Research Lab. Fundación Instituto de Investigaciones Sanitarias-Fundación Jiménez Díaz, Autónoma University. Av. Reyes Católicos 2, 28040, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Tarín
authors.affiliation: 4. Confocal Microscopy Unit, IIS-Gregorio Marañón, C/ Doctor Esquerdo, 4628007 Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Samaniego
authors.affiliation: 5. Pathology Department, Fundación Instituto de Investigaciones Sanitarias-Fundación Jiménez Díaz, Autónoma University. Av. Reyes Católicos 2, 28040, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Cannata
authors.affiliation: 2. CIC biomaGUNE. Paseo Miramón, 182, 20009, San Sebastián, Spain.
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Cano
authors.affiliation: 1. Renal, Vascular and Diabetes Research Lab. Fundación Instituto de Investigaciones Sanitarias-Fundación Jiménez Díaz, Autónoma University. Av. Reyes Católicos 2, 28040, Madrid, Spain.
authors.forename: Juan Manuel Amaro
authors.initials: JM
authors.lastname: Villalobos
authors.affiliation: 6. Department of Nephrology, 12 de Octubre Hospital, 28041 Madrid, Spain.
authors.forename: Ángel Manuel
authors.initials: ÁM
authors.lastname: Sevillano
authors.affiliation: 6. Department of Nephrology, 12 de Octubre Hospital, 28041 Madrid, Spain.
authors.forename: Claudia
authors.initials: C
authors.lastname: Yuste
authors.affiliation: 6. Department of Nephrology, 12 de Octubre Hospital, 28041 Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gutiérrez
authors.affiliation: 6. Department of Nephrology, 12 de Octubre Hospital, 28041 Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Praga
authors.affiliation: 1. Renal, Vascular and Diabetes Research Lab. Fundación Instituto de Investigaciones Sanitarias-Fundación Jiménez Díaz, Autónoma University. Av. Reyes Católicos 2, 28040, Madrid, Spain.; 7. Centre of Biomedical Research in network of Diabetes and Metabolic disease associated (CIBERDEM).
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
authors.affiliation: 1. Renal, Vascular and Diabetes Research Lab. Fundación Instituto de Investigaciones Sanitarias-Fundación Jiménez Díaz, Autónoma University. Av. Reyes Católicos 2, 28040, Madrid, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Moreno
mesh_terms: D058186:Acute Kidney Injury / Q000000981:diagnostic imaging* / Q000503:physiopathology; D000818:Animals; D000906:Antibodies; D015703:Antigens, CD / Q000032:analysis*; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis*; D005290:Ferric Compounds; D006046:Gold; D006801:Humans; D008264:Macrophages / Q000737:chemistry* / Q000276:immunology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D053758:Nanoparticles; D011956:Receptors, Cell Surface / Q000032:analysis*; D012206:Rhabdomyolysis / Q000150:complications*; D013194:Staining and Labeling / Q000379:methods*; D000098902:CD163 Antigen
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D005290:Ferric Compounds; D011956:Receptors, Cell Surface; C000499:ferric oxide; D006046:Gold
keywords: CD163; MRI; acute kidney injury.; gold coated iron oxide nanoparticles; macrophages; rhabdomyolysis