Title :

Serpin b1 defect and increased apoptosis of neutrophils in cohen syndrome neutropenia

Author(s) :

Duplomb, Laurence [Auteur]
Riviere, Julie [Auteur]
Jego, Gaetan [Auteur]
Da Costa, Romain [Auteur]
Hammann, Arlette [Auteur]
Racine, Jessica [Auteur]
Schmitt, Alain [Auteur]
Droin, Nathalie [Auteur]
Capron, Claude [Auteur]
Gougerot-Pocidalo, Marie-Anne [Auteur]
Dubrez, Laurence [Auteur]
Aral, Bernard [Auteur]
Lafon, Arnaud [Auteur]
Edery, Patrick [Auteur]
Ghoumid, Jamal [Auteur]
Blair, Edward M. [Auteur]
El Chehadeh-Djebbar, Salima [Auteur]
Carmignac, Virginie [Auteur]
Thevenon, Julien [Auteur]
Guy, Julien [Auteur]
Girodon, Francois [Auteur]
Bastie, Jean-Noel [Auteur]
Delva, Laurent [Auteur]
Faivre, Laurence [Auteur]
Thauvin-Robinet, Christel [Auteur]
Solary, Eric [Auteur]

Journal title :

Journal of molecular medicine (Berlin, Germany)

Abbreviated title :

J. Mol. Med.

Volume number :

97

Publication date :

2019-05-01

ISSN :

0946-2716

Keyword(s) :

Neutropenia
Cohen syndrome
Serpin B1
Apoptosis

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Cohen syndrome (CS) is a rare genetic disorder due to mutations in VPS13B gene. Among various clinical and biological features, CS patients suffer from inconsistent neutropenia, which is associated with recurrent but minor ...
Show more >Cohen syndrome (CS) is a rare genetic disorder due to mutations in VPS13B gene. Among various clinical and biological features, CS patients suffer from inconsistent neutropenia, which is associated with recurrent but minor infections. We demonstrate here that this neutropenia results from an exaggerate rate of neutrophil apoptosis. Besides this increased cell death, which occurs in the absence of any endoplasmic reticulum stress or defect in neutrophil elastase (ELANE) expression or localization, all neutrophil functions appeared to be normal. We showed a disorganization of the Golgi apparatus in CS neutrophils precursors, that correlates with an altered glycosylation of ICAM-1 in these cells, as evidenced by a migration shift of the protein. Furthermore, a striking decrease in the expression of SERPINB1 gene, which encodes a critical component of neutrophil survival, was detected in CS neutrophils. These abnormalities may account for the excessive apoptosis of neutrophils leading to neutropenia in CS. KEY MESSAGES: Cohen syndrome patients' neutrophils display normal morphology and functions. Cohen syndrome patients' neutrophils have an increased rate of spontaneous apoptosis compared to healthy donors' neutrophils. No ER stress or defective ELA2 expression or glycosylation was observed in Cohen syndrome patients' neutrophils. SerpinB1 expression is significantly decreased in Cohen syndrome neutrophils as well as in VPS13B-deficient cells.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille

Collections :

• Maladies Rares du Développement : Génétique, Régulation et Protéomique (RADEME) - ULR 7364

Submission date :

2021-09-02T07:02:00Z