Theranostics 2016; 6(6):896-914. doi:10.7150/thno.14915

Research Paper

CD163-Macrophages Are Involved in Rhabdomyolysis-Induced Kidney Injury and May Be Detected by MRI with Targeted Gold-Coated Iron Oxide Nanoparticles

Alfonso Rubio-Navarro1*, Mónica Carril2,3*, Daniel Padro2, Melanie Guerrero-Hue1, Carlos Tarín1, Rafael Samaniego4, Pablo Cannata5, Ainhoa Cano2, Juan Manuel Amaro Villalobos1, Ángel Manuel Sevillano6, Claudia Yuste6, Eduardo Gutiérrez6, Manuel Praga6, Jesús Egido1,7, Juan Antonio Moreno1✉

1. Renal, Vascular and Diabetes Research Lab. Fundación Instituto de Investigaciones Sanitarias-Fundación Jiménez Díaz, Autónoma University. Av. Reyes Católicos 2, 28040, Madrid, Spain.
2. CIC biomaGUNE. Paseo Miramón, 182, 20009, San Sebastián, Spain.
3. Ikerbasque, Basque Foundation for Science, 48011, Bilbao, Spain.
4. Confocal Microscopy Unit, IIS-Gregorio Marañón, C/ Doctor Esquerdo, 4628007 Madrid, Spain.
5. Pathology Department, Fundación Instituto de Investigaciones Sanitarias-Fundación Jiménez Díaz, Autónoma University. Av. Reyes Católicos 2, 28040, Madrid, Spain.
6. Department of Nephrology, 12 de Octubre Hospital, 28041 Madrid, Spain
7. Centre of Biomedical Research in network of Diabetes and Metabolic disease associated (CIBERDEM).
* Both authors contributed equally.

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.

Keywords: rhabdomyolysis, CD163, macrophages, gold coated iron oxide nanoparticles, MRI, acute kidney injury.

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How to cite this article:
Rubio-Navarro A, Carril M, Padro D, Guerrero-Hue M, Tarín C, Samaniego R, Cannata P, Cano A, Villalobos JMA, Sevillano ÁM, Yuste C, Gutiérrez E, Praga M, Egido J, Moreno JA. CD163-Macrophages Are Involved in Rhabdomyolysis-Induced Kidney Injury and May Be Detected by MRI with Targeted Gold-Coated Iron Oxide Nanoparticles. Theranostics 2016; 6(6):896-914. doi:10.7150/thno.14915. Available from http://www.thno.org/v06p0896.htm