Macrophage Trafficking as Key Mediator of Adenine-Induced Kidney Injury

Author(s)

Correa-Costa, Matheus ; Braga, Tarcio Teodoro ; Felizardo, Raphael Jose Ferreira ; Andrade-Oliveira, Vinicius ; Regina Perez, Katia ; Midea Cuccovia, Iolanda ; Ioshie Hiyane, Meire ; Santana da Silva, Joao ; Saraiva Camara, Niels Olsen

• Document type: Journal article
• Source: Mediators of Inflammation; v. 2014, p. 12-pg., 2014-01-01.

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. (AU)

• FAPESP's process: 12/02270-2 - New cellular, molecular and immunological mechanisms involved in acute and chronic renal injury: the search for new therapeutical approaches
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/25010-9 - Role of heme oxygenase-1 in autophagy modulation during ischemic renal injury
• Grantee: Matheus Corrêa Costa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral