Cargando…

Immunophenotypical Characterization of M1/M2 Macrophages and Lymphocytes in Cisplatin-Induced Rat Progressive Renal Fibrosis

Renal fibrosis is regarded as the common final pathway leading to chronic kidney diseases; macrophages and myofibroblasts play important roles in the development of fibrosis. F344 rats were injected once with cisplatin (CDDP; 6 mg/kg BW) for renal lesions. Here, immunophenotypical characteristics of...

Descripción completa

Detalles Bibliográficos
Autores principales: Nakagawa, Minto, Karim, Mohammad Rabiul, Izawa, Takeshi, Kuwamura, Mitsuru, Yamate, Jyoji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911194/
https://www.ncbi.nlm.nih.gov/pubmed/33525592
http://dx.doi.org/10.3390/cells10020257
_version_ 1783656283993276416
author Nakagawa, Minto
Karim, Mohammad Rabiul
Izawa, Takeshi
Kuwamura, Mitsuru
Yamate, Jyoji
author_facet Nakagawa, Minto
Karim, Mohammad Rabiul
Izawa, Takeshi
Kuwamura, Mitsuru
Yamate, Jyoji
author_sort Nakagawa, Minto
collection PubMed
description Renal fibrosis is regarded as the common final pathway leading to chronic kidney diseases; macrophages and myofibroblasts play important roles in the development of fibrosis. F344 rats were injected once with cisplatin (CDDP; 6 mg/kg BW) for renal lesions. Here, immunophenotypical characteristics of macrophages and lymphocytes in CDDP-induced rat renal lesions were investigated histopathologically; the CDDP-induced renal lesions consisted of tissue damage at the early-stage, worsen the damage and commencement of interstitial fibrosis at the mid-stage, and progressive fibrosis at the late stage; the KIM-1 expression and α-SMA(+) myofibroblast area reflected renal tubular damage/abnormal regeneration and renal interstitial fibrosis, respectively. CD68(+) M1 macrophages began to increase at the mid-stage, with increased mRNA expressions of M1-related cytokines (INF-γ, TNF-α and IL-6), and then slightly decreased at the late-stage. CD163(+) M2 macrophages showed a gradually increased number at the mid- and late-stages, accompanied by increased TGF-β1 mRNA expression (a fibrogenic factor). Double immunofluorescence using fibrotic samples at the late-stage revealed that 62.0–78.0% of CD68(+) M1 macrophages co-expressed CD163, indicating that M1/M2 macrophages may contribute to progressive renal fibrosis in cooperation; further, MHC class II-expressing macrophages had a tendency towards M1 polarization, whereas CD204-expressing macrophages towards M2 polarization. In addition, CD4(+) and CD8(+) T cells were increased at the late-stage. Collectively, progressive renal interstitial fibrosis may be developed by complicated mechanisms that arose via interaction of M1/M2 macrophages (inflammatory for M1 and anti-inflammatory for M2) and T cells reacting to CD4 (for helper) and CD8 (for cytotoxicity). This study would provide some information on the pathogenesis of renal fibrosis based on inflammatory cells.
format Online
Article
Text
id pubmed-7911194
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-79111942021-02-28 Immunophenotypical Characterization of M1/M2 Macrophages and Lymphocytes in Cisplatin-Induced Rat Progressive Renal Fibrosis Nakagawa, Minto Karim, Mohammad Rabiul Izawa, Takeshi Kuwamura, Mitsuru Yamate, Jyoji Cells Article Renal fibrosis is regarded as the common final pathway leading to chronic kidney diseases; macrophages and myofibroblasts play important roles in the development of fibrosis. F344 rats were injected once with cisplatin (CDDP; 6 mg/kg BW) for renal lesions. Here, immunophenotypical characteristics of macrophages and lymphocytes in CDDP-induced rat renal lesions were investigated histopathologically; the CDDP-induced renal lesions consisted of tissue damage at the early-stage, worsen the damage and commencement of interstitial fibrosis at the mid-stage, and progressive fibrosis at the late stage; the KIM-1 expression and α-SMA(+) myofibroblast area reflected renal tubular damage/abnormal regeneration and renal interstitial fibrosis, respectively. CD68(+) M1 macrophages began to increase at the mid-stage, with increased mRNA expressions of M1-related cytokines (INF-γ, TNF-α and IL-6), and then slightly decreased at the late-stage. CD163(+) M2 macrophages showed a gradually increased number at the mid- and late-stages, accompanied by increased TGF-β1 mRNA expression (a fibrogenic factor). Double immunofluorescence using fibrotic samples at the late-stage revealed that 62.0–78.0% of CD68(+) M1 macrophages co-expressed CD163, indicating that M1/M2 macrophages may contribute to progressive renal fibrosis in cooperation; further, MHC class II-expressing macrophages had a tendency towards M1 polarization, whereas CD204-expressing macrophages towards M2 polarization. In addition, CD4(+) and CD8(+) T cells were increased at the late-stage. Collectively, progressive renal interstitial fibrosis may be developed by complicated mechanisms that arose via interaction of M1/M2 macrophages (inflammatory for M1 and anti-inflammatory for M2) and T cells reacting to CD4 (for helper) and CD8 (for cytotoxicity). This study would provide some information on the pathogenesis of renal fibrosis based on inflammatory cells. MDPI 2021-01-28 /pmc/articles/PMC7911194/ /pubmed/33525592 http://dx.doi.org/10.3390/cells10020257 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nakagawa, Minto
Karim, Mohammad Rabiul
Izawa, Takeshi
Kuwamura, Mitsuru
Yamate, Jyoji
Immunophenotypical Characterization of M1/M2 Macrophages and Lymphocytes in Cisplatin-Induced Rat Progressive Renal Fibrosis
title Immunophenotypical Characterization of M1/M2 Macrophages and Lymphocytes in Cisplatin-Induced Rat Progressive Renal Fibrosis
title_full Immunophenotypical Characterization of M1/M2 Macrophages and Lymphocytes in Cisplatin-Induced Rat Progressive Renal Fibrosis
title_fullStr Immunophenotypical Characterization of M1/M2 Macrophages and Lymphocytes in Cisplatin-Induced Rat Progressive Renal Fibrosis
title_full_unstemmed Immunophenotypical Characterization of M1/M2 Macrophages and Lymphocytes in Cisplatin-Induced Rat Progressive Renal Fibrosis
title_short Immunophenotypical Characterization of M1/M2 Macrophages and Lymphocytes in Cisplatin-Induced Rat Progressive Renal Fibrosis
title_sort immunophenotypical characterization of m1/m2 macrophages and lymphocytes in cisplatin-induced rat progressive renal fibrosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911194/
https://www.ncbi.nlm.nih.gov/pubmed/33525592
http://dx.doi.org/10.3390/cells10020257
work_keys_str_mv AT nakagawaminto immunophenotypicalcharacterizationofm1m2macrophagesandlymphocytesincisplatininducedratprogressiverenalfibrosis
AT karimmohammadrabiul immunophenotypicalcharacterizationofm1m2macrophagesandlymphocytesincisplatininducedratprogressiverenalfibrosis
AT izawatakeshi immunophenotypicalcharacterizationofm1m2macrophagesandlymphocytesincisplatininducedratprogressiverenalfibrosis
AT kuwamuramitsuru immunophenotypicalcharacterizationofm1m2macrophagesandlymphocytesincisplatininducedratprogressiverenalfibrosis
AT yamatejyoji immunophenotypicalcharacterizationofm1m2macrophagesandlymphocytesincisplatininducedratprogressiverenalfibrosis