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Inflammopharmacology

, Volume 26, Issue 2, pp 403–411 | Cite as

CCR2 contributes to the recruitment of monocytes and leads to kidney inflammation and fibrosis development

  • Tarcio Teodoro BragaEmail author
  • Matheus Correa-Costa
  • Reinaldo Correia Silva
  • Mario Costa Cruz
  • Meire Ioshie Hiyane
  • Joao Santana da Silva
  • Katia Regina Perez
  • Iolanda Midea Cuccovia
  • Niels Olsen Saraiva Camara
Original Article

Abstract

Chemokines are a large family of proteins that, once associated to its receptor on leukocytes, stimulate their movement and migration from blood to tissues. Once in the tissue, immune cells trigger inflammation that, when uncontrolled, leads to fibrosis development. Among the immune cells, macrophages take a special role in fibrosis formation, since macrophage depletion reflects less collagen deposition. The majority of tissue macrophages is derived from monocytes, especially monocytes expressing the chemokine receptor CCR2. Here, we investigated the role of infiltrating CCR2+ cells in the development of fibrosis, and specifically, the dynamic of infiltration of these cells into kidneys under chronic obstructive lesion. Using liposome-encapsulated clodronate, we observed that macrophage depletion culminated in less collagen deposition and reduced chemokines milieu that were released in the damaged kidney after obstructive nephropathy. We also obstructed the kidneys of CCL3−/−, CCR2−/−, CCR4−/−, CCR5−/−, and C57BL/6 mice and we found that among all animals, CCR2−/− mice demonstrated the more robust protection, reflected by less inflammatory and Th17-related cytokines and less collagen formation. Next we evaluated the dynamic of CCR2+/rfp cell infiltration and we observed that they adhere onto the vessels at early stages of disease, culminating in increased recruitment of CCR2+/rfp cells at later stages. On the other hand, CCR2rfp/rfp animals exhibited less fibrosis formation and reduced numbers of recruited cells at later stages. We have experimentally demonstrated that inflammatory CCR2+ cells that reach the injured kidney at initial stages after tissue damage are responsible for the fibrotic pattern observed at later time points in the context of UUO.

Keywords

CCR2+ monocytes Fibrosis UUO 

Notes

Acknowledgements

We gratefully acknowledge funding provided by CNPq, Capes, and Fapesp (2014/06992-8 and 2012/02270-2).

Compliance with ethical standards

Conflict of interest

None of the authors have any competing interests.

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Copyright information

© Springer International Publishing 2017

Authors and Affiliations

  • Tarcio Teodoro Braga
    • 1
    Email author
  • Matheus Correa-Costa
    • 1
  • Reinaldo Correia Silva
    • 1
  • Mario Costa Cruz
    • 1
  • Meire Ioshie Hiyane
    • 1
  • Joao Santana da Silva
    • 2
  • Katia Regina Perez
    • 3
  • Iolanda Midea Cuccovia
    • 3
  • Niels Olsen Saraiva Camara
    • 1
    • 4
    • 5
  1. 1.Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IVUniversity of São Paulo (USP)São PauloBrazil
  2. 2.Department of Biochemistry and Immunology, School of Medicine of Ribeirão PretoUniversity of São PauloRibeirão PretoBrazil
  3. 3.Department of BiochemistryInstitute of Chemistry University of São Paulo (USP)São PauloBrazil
  4. 4.Laboratory of Clinical and Experimental Immunology, Nephrology DivisionFederal University of São Paulo (UNIFESP)São PauloBrazil
  5. 5.Renal Pathophysiology Laboratory (LIM16), Faculty of MedicineUniversity of São PauloSão PauloBrazil

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