Particulate matter (PM10) induces in vitro activation of human neutrophils, and lung histopathological alterations in a mouse model

The epidemiological association between exposure to particulate matter (PM10) and various respiratory and cardiovascular problems is well known, but the mechanisms driving these efects remain unclear. Neutrophils play an essential role in immune defense against foreign agents and also participate in...

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Autores:
Valderrama, Andrés
Ortiz‑Hernández, Paul
Agraz‑Cibrián, Juan Manuel
Tabares‑Guevara, Jorge H.
Gómez Gallego, Diana Maryory
Zambrano‑Zaragoza, José Francisco
Taborda, NataliaA.
Hernández López, Juan Carlos
Tipo de recurso:
Article of investigation
Fecha de publicación:
2022
Institución:
Universidad Cooperativa de Colombia
Repositorio:
Repositorio UCC
Idioma:
OAI Identifier:
oai:repository.ucc.edu.co:20.500.12494/45975
Acceso en línea:
https://hdl.handle.net/20.500.12494/45975
Palabra clave:
Particulate matter
neutrophils
lung
mouse model
Rights
openAccess
License
Atribución
Description
Summary:The epidemiological association between exposure to particulate matter (PM10) and various respiratory and cardiovascular problems is well known, but the mechanisms driving these efects remain unclear. Neutrophils play an essential role in immune defense against foreign agents and also participate in the development of infammatory responses. However, the role of these cells in the PM10 induced infammatory response is not yet fully established. Thus, this study aims to evaluate the efect of PM10 on the neutrophil-mediated infammatory response. For this, neutrophils from healthy adult human donors were in vitro exposed to diferent concentrations of PM10. The cell viability and cytotoxic activity were evaluated by MTT. LDH, propidium iodide and reactive oxygen species (ROS) were quantifed by fow 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 quantifed by ELISA. Fluorescence microscopy was used to evaluate neutrophil extracellular traps (NETs) release. The in vivo infammatory responses were assessed in BALB/c mice exposed to PM10 by histopathology and RT-PCR. The analysis shows that ­PM10 exposure induced a cytotoxic efect 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 infltration in bronchoalveolar lavage fuid (BALF), histopathological changes with infammatory cell infltration, and CXCL1 expression were observed in PM10-treated mice. The results suggest that lung infammation in response to PM10 could be mediated by neutrophils activation. In this case, these cells migrate to the lungs and release pro-infamatory mediators, including ROS, IL-8, and NETs. Thus, contributing to the exacerbation of respiratory pathologies, such as allergies, infectious and obstructive diseases