Exosomes from eosinophils autoregulate and promote eosinophil functions

J Leukoc Biol. 2017 May;101(5):1191-1199. doi: 10.1189/jlb.3AB0516-233RR. Epub 2017 Jan 17.

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.

Keywords: eosinophil adhesion; eosinophil migration; oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Apoptosis / immunology
  • Asthma / blood
  • Asthma / immunology*
  • Asthma / pathology
  • Case-Control Studies
  • Cell Adhesion / immunology
  • Chemotaxis, Leukocyte
  • Eosinophils / immunology*
  • Eosinophils / metabolism
  • Eosinophils / pathology
  • Exosomes / chemistry
  • Exosomes / immunology*
  • Exosomes / pathology
  • Female
  • Gene Expression Regulation
  • Humans
  • Immunoglobulin E / blood
  • Integrin alpha2 / genetics
  • Integrin alpha2 / immunology
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / immunology
  • Male
  • Middle Aged
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / immunology*
  • Reactive Oxygen Species / immunology*
  • Reactive Oxygen Species / metabolism

Substances

  • ICAM1 protein, human
  • Integrin alpha2
  • Reactive Oxygen Species
  • Intercellular Adhesion Molecule-1
  • Nitric Oxide
  • Immunoglobulin E