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Title: CCR2 contributes to the recruitment of monocytes and leads to kidney inflammation and fibrosis development
Authors: Braga, Tarcio Teodoro
Correa-Costa, Matheus
Silva, Reinaldo Correia
Cruz, Mario Costa
Hiyane, Meire Ioshie [UNIFESP]
Silva, Joao Santana da
Perez, Katia Regina
Cuccovia, Iolanda Midea
Câmara, Niels Olsen Saraiva [UNIFESP]
Keywords: CCR2(+) monocytes
Issue Date: 2018
Publisher: Springer Basel Ag
Citation: Inflammopharmacology. Basel, v. 26, n. 2, p. 403-411, 2018.
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, CCR2(rfp/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.
ISSN: 0925-4692
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