Particulate matter (PM10) induces in vitro activation of human neutrophils, and lung histopathological alterations in a mouse model
Abstract The epidemiological association between exposure to particulate matter (PM10) and various respiratory and cardiovascular problems is well known, but the mechanisms driving these effects remain unclear. Neutrophils play an essential role in immune defense against foreign agents and also part...
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Nature Portfolio
2022-05-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-022-11553-6 |
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author | Andrés Valderrama Paul Ortiz-Hernández Juan Manuel Agraz-Cibrián Jorge H. Tabares-Guevara Diana M. Gómez José Francisco Zambrano-Zaragoza Natalia A. Taborda Juan C. Hernandez |
author_facet | Andrés Valderrama Paul Ortiz-Hernández Juan Manuel Agraz-Cibrián Jorge H. Tabares-Guevara Diana M. Gómez José Francisco Zambrano-Zaragoza Natalia A. Taborda Juan C. Hernandez |
author_sort | Andrés Valderrama |
collection | DOAJ |
description | Abstract The epidemiological association between exposure to particulate matter (PM10) and various respiratory and cardiovascular problems is well known, but the mechanisms driving these effects remain unclear. Neutrophils play an essential role in immune defense against foreign agents and also participate in the development of inflammatory responses. However, the role of these cells in the PM10 induced inflammatory response is not yet fully established. Thus, this study aims to evaluate the effect of PM10 on the neutrophil-mediated inflammatory response. For this, neutrophils from healthy adult human donors were in vitro exposed to different concentrations of PM10. The cell viability and cytotoxic activity were evaluated by MTT. LDH, propidium iodide and reactive oxygen species (ROS) were quantified by flow cytometry. Interleukin 8 (IL-8) expression, peptidyl arginine deiminase 4 (PAD4), myeloperoxidase (MPO), and neutrophil elastase (NE) expression were measured by RT-PCR. IL-8 was also quantified by ELISA. Fluorescence microscopy was used to evaluate neutrophil extracellular traps (NETs) release. The in vivo inflammatory responses were assessed in BALB/c mice exposed to PM10 by histopathology and RT-PCR. The analysis shows that PM10 exposure induced a cytotoxic effect on neutrophils, evidenced by necrosis and LDH release at high PM10 concentrations. ROS production, IL-8, MPO, NE expression, and NETs release were increased at all PM10 concentrations assessed. Neutrophil infiltration in bronchoalveolar lavage fluid (BALF), histopathological changes with inflammatory cell infiltration, and CXCL1 expression were observed in PM10-treated mice. The results suggest that lung inflammation in response to PM10 could be mediated by neutrophils activation. In this case, these cells migrate to the lungs and release pro-inflamatory mediators, including ROS, IL-8, and NETs. Thus, contributing to the exacerbation of respiratory pathologies, such as allergies, infectious and obstructive diseases. |
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language | English |
last_indexed | 2024-04-12T16:47:28Z |
publishDate | 2022-05-01 |
publisher | Nature Portfolio |
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spelling | doaj.art-d14034fab4684831adcb6a34cc1a456a2022-12-22T03:24:32ZengNature PortfolioScientific Reports2045-23222022-05-0112111110.1038/s41598-022-11553-6Particulate matter (PM10) induces in vitro activation of human neutrophils, and lung histopathological alterations in a mouse modelAndrés Valderrama0Paul Ortiz-Hernández1Juan Manuel Agraz-Cibrián2Jorge H. Tabares-Guevara3Diana M. Gómez4José Francisco Zambrano-Zaragoza5Natalia A. Taborda6Juan C. Hernandez7Infettare, Facultad de Medicina, Universidad Cooperativa de ColombiaUnidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Universidad Autónoma de NayaritUnidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Universidad Autónoma de NayaritInfettare, Facultad de Medicina, Universidad Cooperativa de ColombiaInfettare, Facultad de Medicina, Universidad Cooperativa de ColombiaUnidad Académica de Ciencias Químico Biológicas y Farmacéuticas, Universidad Autónoma de NayaritGrupo de Investigaciones Biomédicas Uniremington, Programa de Medicina, Facultad de Ciencias de La Salud, Corporación Universitaria RemingtonInfettare, Facultad de Medicina, Universidad Cooperativa de ColombiaAbstract The epidemiological association between exposure to particulate matter (PM10) and various respiratory and cardiovascular problems is well known, but the mechanisms driving these effects remain unclear. Neutrophils play an essential role in immune defense against foreign agents and also participate in the development of inflammatory responses. However, the role of these cells in the PM10 induced inflammatory response is not yet fully established. Thus, this study aims to evaluate the effect of PM10 on the neutrophil-mediated inflammatory response. For this, neutrophils from healthy adult human donors were in vitro exposed to different concentrations of PM10. The cell viability and cytotoxic activity were evaluated by MTT. LDH, propidium iodide and reactive oxygen species (ROS) were quantified by flow cytometry. Interleukin 8 (IL-8) expression, peptidyl arginine deiminase 4 (PAD4), myeloperoxidase (MPO), and neutrophil elastase (NE) expression were measured by RT-PCR. IL-8 was also quantified by ELISA. Fluorescence microscopy was used to evaluate neutrophil extracellular traps (NETs) release. The in vivo inflammatory responses were assessed in BALB/c mice exposed to PM10 by histopathology and RT-PCR. The analysis shows that PM10 exposure induced a cytotoxic effect on neutrophils, evidenced by necrosis and LDH release at high PM10 concentrations. ROS production, IL-8, MPO, NE expression, and NETs release were increased at all PM10 concentrations assessed. Neutrophil infiltration in bronchoalveolar lavage fluid (BALF), histopathological changes with inflammatory cell infiltration, and CXCL1 expression were observed in PM10-treated mice. The results suggest that lung inflammation in response to PM10 could be mediated by neutrophils activation. In this case, these cells migrate to the lungs and release pro-inflamatory mediators, including ROS, IL-8, and NETs. Thus, contributing to the exacerbation of respiratory pathologies, such as allergies, infectious and obstructive diseases.https://doi.org/10.1038/s41598-022-11553-6 |
spellingShingle | Andrés Valderrama Paul Ortiz-Hernández Juan Manuel Agraz-Cibrián Jorge H. Tabares-Guevara Diana M. Gómez José Francisco Zambrano-Zaragoza Natalia A. Taborda Juan C. Hernandez Particulate matter (PM10) induces in vitro activation of human neutrophils, and lung histopathological alterations in a mouse model Scientific Reports |
title | Particulate matter (PM10) induces in vitro activation of human neutrophils, and lung histopathological alterations in a mouse model |
title_full | Particulate matter (PM10) induces in vitro activation of human neutrophils, and lung histopathological alterations in a mouse model |
title_fullStr | Particulate matter (PM10) induces in vitro activation of human neutrophils, and lung histopathological alterations in a mouse model |
title_full_unstemmed | Particulate matter (PM10) induces in vitro activation of human neutrophils, and lung histopathological alterations in a mouse model |
title_short | Particulate matter (PM10) induces in vitro activation of human neutrophils, and lung histopathological alterations in a mouse model |
title_sort | particulate matter pm10 induces in vitro activation of human neutrophils and lung histopathological alterations in a mouse model |
url | https://doi.org/10.1038/s41598-022-11553-6 |
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