title: Exosomes from eosinophils autoregulate and promote eosinophil functions.
abstract: Eosinophils are able to secrete exosomes that have an undefined role in asthma pathogenesis. We hypothesized that exosomes released by eosinophils autoregulate and promote eosinophil function. Eosinophils of patients with asthma (n= 58) and healthy volunteers (n= 16) were purified from peripheral blood, and exosomes were isolated and quantified from eosinophils of the asthmatic and healthy populations. Apoptosis, adhesion, adhesion molecules expression, and migration assays were performed with eosinophils in the presence or absence of exosomes from healthy and asthmatic individuals. Reactive oxygen species (ROS) were evaluated by flow cytometry with an intracellular fluorescent probe and nitric oxide (NO) and a colorimetric kit. In addition, exosomal proteins were analyzed by mass spectrometry. Eosinophil-derived exosomes induced an increase in NO and ROS production on eosinophils. Moreover, exosomes could act as a chemotactic factor on eosinophils, and they produced an increase in cell adhesion, giving rise to a specific augmentation of adhesion molecules, such as ICAM-1 and integrin α2. Protein content between exosomes from healthy and asthmatic individuals seems to be similar in both groups. In conclusion, we found that exosomes from the eosinophils of patients with asthma could modify several specific eosinophil functions related to asthma pathogenesis and that they could contribute fundamentally to the development and maintenance of asthma.
authors.affiliation: Department of Immunology, IIS-Fundación Jiménez Díaz, Madrid, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Cañas
authors.affiliation: Department of Immunology, IIS-Fundación Jiménez Díaz, Madrid, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Sastre
authors.affiliation: Department of Immunology, IIS-Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Carla
authors.initials: C
authors.lastname: Mazzeo
authors.affiliation: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.|Department of Allergy, IIS-Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Fernández-Nieto
authors.affiliation: Department of Immunology, IIS-Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Rodrigo-Muñoz
authors.affiliation: Department of Immunology, IIS-Fundación Jiménez Díaz, Madrid, Spain.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: González-Guerra
authors.affiliation: Department of Biochemistry, Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain; and.
authors.forename: Manuel
authors.initials: M
authors.lastname: Izquierdo
authors.affiliation: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.|Department of Allergy, Hospital La Paz-Institute for Health Research (IdiPAZ), Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Barranco
authors.affiliation: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.|Department of Allergy, Hospital La Paz-Institute for Health Research (IdiPAZ), Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Quirce
authors.affiliation: CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.|Department of Allergy, IIS-Fundación Jiménez Díaz, Madrid, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Sastre
authors.affiliation: Department of Immunology, IIS-Fundación Jiménez Díaz, Madrid, Spain; vpozo@fjd.es.|CIBER de Enfermedades Respiratorias (CIBERES), Madrid, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Del Pozo
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000276:immunology; D001249:Asthma / Q000097:blood / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D004804:Eosinophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D055354:Exosomes / Q000737:chemistry / Q000276:immunology* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D039421:Integrin alpha2 / Q000235:genetics / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000276:immunology* / Q000378:metabolism
chemical_list: C573420:ICAM1 protein, human; D039421:Integrin alpha2; D017382:Reactive Oxygen Species; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D007073:Immunoglobulin E
keywords: eosinophil adhesion; eosinophil migration; oxidative stress