Artículo
Regulation and directed inhibition of ECP production by human neutrophils
Autor/es | Vega Rioja, Antonio
Chacón, Pedro Fernández Delgado, Lourdes Doukkali, Bouchra Valle Rodríguez, Alberto del Perkins, James R. Ranea, Juan A. G. Domínguez Cereijo, Leticia Pérez-Machuca, Beatriz María Palacios, Ricardo Rodríguez, David Monteseirín Mateo, Francisco Javier Ribas Pérez, David |
Departamento | Universidad de Sevilla. Departamento de Estomatología |
Fecha de publicación | 2022-11-28 |
Fecha de depósito | 2023-05-16 |
Publicado en |
|
Resumen | Background: Neutrophils are involved in the pathophysiology of allergic asthma, where the Eosinophil Cationic Protein (ECP) is a critical inflammatory mediator. Although ECP production is attributed to eosinophils, we ... Background: Neutrophils are involved in the pathophysiology of allergic asthma, where the Eosinophil Cationic Protein (ECP) is a critical inflammatory mediator. Although ECP production is attributed to eosinophils, we reported that ECP is also present in neutrophils from allergic patients where, in contrast to eosinophils, it is produced in an IgE-dependent manner. Given the key role of ECP in asthma, we investigated the molecular mechanisms involved in ECP production as well as the effects induced by agonists and widely used clinical approaches. We also analyzed the correlation between ECP production and lung function. Methods: Neutrophils from allergic asthmatic patients were challenged with allergens, alone or in combination with cytokines, in the presence of cell-signaling inhibitors and clinical drugs. We analyzed ECP levels by ELISA and confocal microscopy. Lung function was assessed by spirometry. Results: IgE-mediated ECP release is dependent on phosphoinositide 3-kinase, the extracellular signal-regulated kinase (ERK1/2) and the production of reactive oxygen species by NADPH-oxidase. Calcineurin phosphatase and the transcription factor NFAT are also involved. ECP release is enhanced by the cytokines interleukin (IL)-5 and granulocyte macrophage-colony stimulating factor, and inhibited by interferon-γ, IL-10, clinical drugs (formoterol, tiotropium and budesonide) and allergen-specific IT. We also found an inverse correlation between asthma severity and ECP levels. Conclusions: Our results suggest the molecular pathways involved in ECP production and potential therapeutic targets. We also provide a new method to evaluate disease severity in asthmatic patients based on the quantification of in vitro ECP production by peripheral neutrophils. |
Agencias financiadoras | Servicio Andaluz de Salud European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) Fundacion Alergol Instituto de Salud Carlos III (FIS-Redes Temáticas y Centros de Investigación Cooperativa ARADYAL) Ministerio de Economia y Competitividad (Proyectos I+D+i para Jovenes Investigadores) Consejería de Sanidad y Familias (Junta de Andalucía) |
Identificador del proyecto | C-0060-2018
RD16/0006/0035 SAF2014-60649-JIN RH-0129-2020 |
Cita | Vega Rioja, A., Chacón, P., Fernández Delgado, L., Doukkali, B., Valle Rodríguez, A.d., Perkins, J.R.,...,Ribas Pérez, D. (2022). Regulation and directed inhibition of ECP production by human neutrophils. Frontiers in Immunology, 13, 1015529. https://doi.org/10.3389/fimmu.2022.1015529. |
Ficheros | Tamaño | Formato | Ver | Descripción |
---|---|---|---|---|
Regulation and directed inhibition ... | 6.634Mb | [PDF] | Ver/ | |