Title :

Eosinophil cytolysis on Immunoglobulin G is associated with microtubule formation and suppression of rho-associated protein kinase signalling.

Author(s) :

Esnault, Stephane [Auteur]
University of Wisconsin-Madison
Leet, Jonathan P [Auteur]
University of Wisconsin-Madison
Johansson, Mats W [Auteur]
University of Wisconsin School of Medicine and Public Health
Barretto, Karina T [Auteur]
University of Wisconsin School of Medicine and Public Health
Fichtinger, Paul S [Auteur]
University of Wisconsin-Madison
Fogerty, Frances J [Auteur]
University of Wisconsin School of Medicine and Public Health
Bernau, Ksenija [Auteur]
University of Wisconsin-Madison
Mathur, Sameer K [Auteur]
University of Wisconsin-Madison
Mosher, Deane F [Auteur]
University of Wisconsin School of Medicine and Public Health
Sandbo, Nathan [Auteur]
University of Wisconsin-Madison
Jarjour, Nizar N [Auteur]
University of Wisconsin-Madison

Journal title :

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

Abbreviated title :

Clin Exp Allergy

Volume number :

50

Pages :

198-212

Publisher :

Wiley

Publication date :

2020-02-01

ISSN :

1365-2222

English keyword(s) :

Eosinophils
Humans
Immunoglobulin G
Interleukin-3
MAP Kinase Signaling System
Microtubule-Associated Proteins
Microtubules
Reactive Oxygen Species
Receptors, IgG
rho-Associated Kinases
Eosinophil
IL3
adhesion
cytolysis
degranulation
immunoglobulin G
microtubule
priming

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

The presence of eosinophils in the airway is associated with asthma severity and risk of exacerbations. Cell-free eosinophil granules are found in tissues in eosinophilic diseases, including asthma. This suggests that ...
Show more >The presence of eosinophils in the airway is associated with asthma severity and risk of exacerbations. Cell-free eosinophil granules are found in tissues in eosinophilic diseases, including asthma. This suggests that eosinophils have lysed and released cellular content, likely harming tissues. The present study explores the mechanism of CD32- and αMß2 integrin-dependent eosinophil cytolysis of IL3-primed blood eosinophils seeded on heat-aggregated immunoglobulin G (HA-IgG). Cytoskeletal events and signalling pathways potentially involved in cytolysis were assessed using inhibitors. The level of activation of the identified events and pathways involved in cytolysis was measured. In addition, the links between these identified pathways and changes in degranulation (exocytosis) and adhesion were analysed. Cytolysis of IL3-primed eosinophils was dependent on the production of reactive oxygen species (ROS) and downstream phosphorylation of p-38 MAPK. In addition, formation of microtubule (MT) arrays was necessary for cytolysis and was accompanied by changes in MT dynamics as measured by phosphorylation status of stathmin and microtubule-associated protein 4 (MAP4), the latter of which was regulated by ROS production. Reduced ROCK signalling preceded cytolysis, which was associated with eosinophil adhesion and reduced migration. In this CD32- and αMß2 integrin-dependent adhesion model, lysing eosinophils exhibit reduced migration and ROCK signalling, as well as both MT dynamic changes and p-38 phosphorylation downstream of ROS production. We propose that interfering with these pathways would modulate eosinophil cytolysis and subsequent eosinophil-driven tissue damage.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Autres travaux scientifiques

Submission date :

2023-10-21T11:45:17Z
2023-12-06T10:53:58Z
2024-02-15T08:05:10Z
2024-02-15T08:06:30Z