Project name: Project category: Kind of research: Country: Principle investigator:

Etude des mécanismes moléculaires contrôlant l’activation de la NADPH-oxydase et la survie des neutrophiles dans la mucoviscidose: vers de nouvelles pistes thérapeutiques ciblées

France Véronique Witko-Sarsat
Status: Ongoing

Neutrophils are professional phagocytic cells that are able to phagocytose and destroy infectious agents through oxygen-dependent or -independent mechanisms. They are key actors in anti-infectious host defense that can modulate the immune response but are also inflammatory cells that can mediate tissue damage. As a result, their activation and especially the production of reactive oxygen species (ROS) and their apoptosis should be highly controlled. Thereafter, macrophages phagocytose apoptotic neutrophils to eliminate them from the site of inflammation. This latter step should be tightly regulated because it is a key step in the resolution of inflammation. In the neutrophil-dominated inflammation associated with cystic fibrosis (CF), neutrophils are hyperactivated by several inflammatory mediators and especially by interleukin-8 or Pseudomonas aeruginosa-derived products and persist in the patients airways. Neutrophil persistance within airways constitutes an important factor in a patient’s prognosis. We have recently described that PCNA, a key protein originaly described in nucleus for its involvement in DNA replication and reparation, was a pivotal element in the control of the balance survival/apoptosis of neutrophils. In neutrophils, PCNA is building a cytosolic scaffold that associate several proteins aimed at maintaining their survival.
The aim of the study is to decipher the molecular mechanisms the relationships between activation and survival of neutrophils. We believe that neutrophil apoptosis constitutes a potential target for anti-inflammatory therapy and identification of proteins that control neutrophil activation and survival represent a promising avenue of research.

Project amount (€): 43.910

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