cepia

Clinical Epidemiology and Ageing

CD24-triggered caspase-dependent apoptosis via mitochondrial membrane depolarization and reactive oxygen species production of human neutrophils is impaired in sepsis.

Parlato M, Souza-Fonseca-Guimaraes F, Philippart F, Misset B, Adib-Conquy M, Cavaillon J-M J Immunol. 2014;192(5):2449-59.

<p>Apoptosis is the most common pathway of neutrophil death under both physiological and inflammatory conditions. In this study, we describe an apoptotic pathway in human neutrophils that is triggered via the surface molecule CD24. In normal neutrophils, CD24 ligation induces death through depolarization of the mitochondrial membrane in a manner dependent on caspase-3 and caspase-9 and reactive oxygen species. Proinflammatory cytokines such as TNF-α, IFN-γ, and GM-CSF upregulated the expression of CD24 in vitro, favoring the emergence of a new CD16(high)/CD24(high) subset of cultured neutrophils. We observed that CD24 expression (at both mRNA and protein levels) was significantly downregulated in neutrophils from sepsis patients but not from patients with systemic inflammatory response syndrome. This downregulation was reproduced by incubation of neutrophils from healthy controls with corticosteroids or with plasma collected from sepsis patients, but not with IL-10 or TGF-β. Decreased CD24 expression observed on sepsis neutrophils was associated with lack of functionality of the molecule, because cross-ligation of CD24 failed to trigger apoptosis in neutrophils from sepsis patients. Our results suggest a novel aspect of CD24-mediated immunoregulation and represent, to our knowledge, the first report showing the role of CD24 in the delayed/defective cell death in sepsis. </p>

MeSH terms: Apoptosis; Caspases; CD24 Antigen; Cytokines; Down-Regulation; Female; GPI-Linked Proteins; Humans; Male; Membrane Potential, Mitochondrial; Mitochondrial Membranes; Neutrophils; Reactive Oxygen Species; Receptors, IgG; RNA, Messenger; Sepsis
DOI: 10.4049/jimmunol.1301055

Ajouter un commentaire

9 + 0 =