Phagocytes and Oxidative Stress
Laura Baciou (Senior Researcher), Chantal Houée (Associate Professor), Tania Bizouarn (Researcher-HDR), Marie Erard (Professor), Oliver Nüsse (Professor), Hadrien Jalaber (Research Assistant)
Alumni: Sophie Dupré-Crochet (Professor at UVSQ since 2023), Sana Aimeur (PhD Candidate 2020–2023), Stephenson Boakye Owusu (PhD Candidate 2018–2021), Hana Illichova Valenta (PhD Candidate 2017–2020), Elodie Hudik (Research Assistant)
Our goal is to explore the response of phagocytes (neutrophils) subjected to oxidative stress. In certain pathological contexts, an excessive immune and inflammatory response can occur, leading to the overproduction of extracellular ROS due to an accumulation of active neutrophils (immune system overactivation), thus exposing these cells or surrounding tissues to a highly oxidative environment. This situation can also arise during radiation exposure in a diagnostic or therapeutic context. To simulate oxidative stress, we irradiated neutrophils with controlled doses and durations of gamma radiation (60Cobalt). We observed significant degranulation in irradiated phagocytes, with the accumulation of NADPH oxidase membrane components at the cytoplasmic membrane [Owusu2022]. Although neutrophils demonstrated surprising radio-resistance, irradiation nonetheless resulted in pre-activation (partial phosphorylation of p47phox), which led to an amplified immune response [Owusu2021].
To further investigate ROS-mediated feedback on NADPH oxidase, we developed "ROS factory" cells, which are COS7 cells transfected with a chimeric protein capable of generating ROS through a constitutively active NADPH oxidase [Masoud2017]. In these cells, we explored in detail the membrane-level consequences of excessive and uncontrolled ROS production[Valenta2022]. These cells now allow us to validate new ROS probes for imaging purposes [Gatin2021].