title: Macrophage trafficking as key mediator of adenine-induced kidney injury.
abstract: Macrophages play a special role in the onset of several diseases, including acute and chronic kidney injuries. In this sense, tubule interstitial nephritis (TIN) represents an underestimated insult, which can be triggered by different stimuli and, in the absence of a proper regulation, can lead to fibrosis deposition. Based on this perception, we evaluated the participation of macrophage recruitment in the development of TIN. Initially, we provided adenine-enriched food to WT and searched for macrophage presence and action in the kidney. Also, a group of animals were depleted of macrophages with the clodronate liposome while receiving adenine-enriched diet. We collected blood and renal tissue from these animals and renal function, inflammation, and fibrosis were evaluated. We observed higher expression of chemokines in the kidneys of adenine-fed mice and a substantial protection when macrophages were depleted. Then, we specifically investigated the role of some key chemokines, CCR5 and CCL3, in this TIN experimental model. Interestingly, CCR5 KO and CCL3 KO animals showed less renal dysfunction and a decreased proinflammatory profile. Furthermore, in those animals, there was less profibrotic signaling. In conclusion, we can suggest that macrophage infiltration is important for the onset of renal injury in the adenine-induced TIN.
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, University of São Paulo, Institute of Biomedical Sciences, 05508-900 São Paulo, SP, Brazil.
authors.forename: Matheus
authors.identifier: 0000-0003-3364-4390
authors.initials: M
authors.lastname: Correa-Costa
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, University of São Paulo, Institute of Biomedical Sciences, 05508-900 São Paulo, SP, Brazil.
authors.forename: Tárcio Teodoro
authors.initials: TT
authors.lastname: Braga
authors.affiliation: Laboratory of Clinical and Experimental Immunology, Nephrology Division, Federal University of São Paulo, 04023-900 São Paulo, SP, Brazil.
authors.forename: Raphael José Ferreira
authors.initials: RJ
authors.lastname: Felizardo
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, University of São Paulo, Institute of Biomedical Sciences, 05508-900 São Paulo, SP, Brazil.
authors.forename: Vinícius
authors.initials: V
authors.lastname: Andrade-Oliveira
authors.affiliation: Department of Biophysics, Federal University of São Paulo, 04023-062 São Paulo, SP, Brazil.
authors.forename: Katia Regina
authors.identifier: 0000-0001-9612-1816
authors.initials: KR
authors.lastname: Perez
authors.affiliation: Institute of Chemistry, Department of Biochemistry, University of São Paulo, 05508-000 São Paulo, SP, Brazil.
authors.forename: Iolanda Midea
authors.identifier: 0000-0001-8285-7419
authors.initials: IM
authors.lastname: Cuccovia
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, University of São Paulo, Institute of Biomedical Sciences, 05508-900 São Paulo, SP, Brazil.
authors.forename: Meire Ioshie
authors.initials: MI
authors.lastname: Hiyane
authors.affiliation: Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, 14049-900 Ribeirão Preto, SP, Brazil.
authors.forename: João Santana
authors.initials: JS
authors.lastname: da Silva
authors.affiliation: Laboratory of Transplantation Immunobiology, Department of Immunology, University of São Paulo, Institute of Biomedical Sciences, 05508-900 São Paulo, SP, Brazil ; Laboratory of Clinical and Experimental Immunology, Nephrology Division, Federal University of São Paulo, 04023-900 São Paulo, SP, Brazil.
authors.forename: Niels Olsen Saraiva
authors.initials: NO
authors.lastname: Câmara
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D000225:Adenine / Q000633:toxicity*; D000818:Animals; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009395:Nephritis, Interstitial / Q000378:metabolism; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*
chemical_list: C000592874:CCR5 protein, mouse; D054405:Chemokine CCL3; D019713:Receptors, CCR5; D000225:Adenine