title: IL-3 up-regulates and activates human eosinophil CD32 and αMβ2 integrin causing degranulation.
abstract: BACKGROUND
  Eosinophils contribute to the pathogenesis of multiple diseases, including asthma. Treatment with antibodies targeting IL-5 or IL-5 receptor α reduces the frequency of asthma exacerbations. Eosinophil receptors for IL-5 share a common ß-chain with IL-3 and GM-CSF receptors. We recently reported that IL-3 is more potent than IL-5 or GM-CSF in maintaining the ERK/p90S6K/RPS6 ribosome-directed signaling pathway, leading to increased protein translation.
  
  
  OBJECTIVE
  We aimed to determine disease-relevant consequences of prolonged eosinophil stimulation with IL-3.
  
  
  RESULTS
  Human blood eosinophils were used to establish the impact of activation with IL-3 on IgG-driven eosinophil degranulation. When compared to IL-5, continuing exposure to IL-3 further induced degranulation of eosinophils on aggregated IgG via increased production and activation of both CD32 (low affinity IgG receptor) and αMß2 integrin. In addition, unlike IL-5 or GM-CSF, IL-3 induced expression of CD32B/C (FCGRIIB/C) subtype proteins, without changing CD32A (FCGRIIA) protein and CD32B/C mRNA expression levels. Importantly, these in vitro IL-3-induced modifications were recapitulated in vivo on airway eosinophils.
  
  
  CONCLUSIONS
  We observed for the first time upregulation of CD32B/C on eosinophils, and identified IL-3 as a potent inducer of CD32- and αMß2-mediated eosinophil degranulation.
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
authors.forename: S
authors.identifier: http://orcid.org/0000-0001-7238-8671
authors.initials: S
authors.lastname: Esnault
authors.affiliation: Department of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Johansson
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Kelly
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Koenderman
authors.affiliation: Department of Biomolecular Chemistry, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.|Division of Hematology and Oncology, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Mosher
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
authors.forename: N N
authors.initials: NN
authors.lastname: Jarjour
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015415:Biomarkers; D015550:Cell Degranulation / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007377:Interleukin-3 / Q000378:metabolism* / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000378:metabolism*; D017452:Receptors, IgG / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D007377:Interleukin-3; D016177:Macrophage-1 Antigen; D017452:Receptors, IgG
keywords: CD32; IL-3; allergen challenge; degranulation; eosinophils