PT  - JOURNAL ARTICLE
AU  - Weisenburger-Lile, David
AU  - Dong, Yuan
AU  - Yger, Marion
AU  - Weisenburger, Gaëlle
AU  - Polara, Giulia Frasca
AU  - Chaigneau, Thomas
AU  - Ochoa, Riccardo Zapata
AU  - Marro, Beatrice
AU  - Lapergue, Bertrand
AU  - Alamowitch, Sonia
AU  - Elbim, Carole
TI  - Harmful neutrophil subsets in patients with ischemic stroke
AID  - 10.1212/NXI.0000000000000571
DP  - 2019 Jul 01
TA  - Neurology - Neuroimmunology Neuroinflammation
PG  - e571
VI  - 6
IP  - 4
4099  - http://nn.neurology.org/content/6/4/e571.short
4100  - http://nn.neurology.org/content/6/4/e571.full
SO  - Neurol Neuroimmunol Neuroinflamm2019 Jul 01; 6
AB  - Objective To better understand the functional state of circulating neutrophils in patients with ischemic stroke (IS) for planning future clinical trials.Methods We analyzed by flow cytometry activation state of circulating neutrophils and the distribution of neutrophil peripheral subsets in 41 patients with acute IS less than 6 hours before admission and compared them with 22 age-matched healthy controls.Results Our results demonstrated continuous basal hyperactivation of circulating neutrophils during acute IS, characterized by lower l-selectin expression and higher CD11b expression at the cell surface, increased ROS production by neutrophils, and greater circulating levels of neutrophil elastase. Neutrophil hyperactivation was associated with deregulation of the equilibrium between apoptotic and necrotic. Patients also had higher percentages than controls of the overactive senescent (CXCR4bright/CD62Ldim) neutrophil subset and increased percentage of neutrophils with a reverse transendothelial migration (CD54highCXCR1low) phenotype. Importantly, neutrophil alterations were associated with the clinical severity of the stroke, evaluated by its NIH Stroke Scale score.Conclusion Altogether, our results indicate that during acute IS, the inflammatory properties of circulating neutrophils rise, associated with the expansion of harmful neutrophil subsets. These changes in neutrophil homeostasis, associated with disease severity, may play an instrumental role by contributing to systemic inflammation and to the blood-brain barrier breakdown. Our findings highlight new potential therapeutic approaches of stroke by rebalancing the ratio of senescent to immunosuppressive neutrophils or decreasing reverse neutrophil transmigration or both.AAD=amino-actinomycin D; ANOVA=analysis of variance; APC=allophycocyanine; BBB=blood-brain barrier; DAMP=danger-associated molecular pattern; fMLP=N-formylmethionyl-leucyl-phenylalanine; HC=healthy control; HE=hydroethidine; HMGB=high-mobility group box; IS=ischemic stroke; LPS=lipopolysaccharide; MMP=matrix metalloproteinase; MPO=myeloperoxidase; NET=neutrophil extracellular trap; NIHSS=NIH Stroke Scale; NLR=Nod-like receptor; PBS=phosphate buffered saline; PMN=polymorphonuclear neutrophil; ROS=reactive oxygen species; rTEM=reverse transendothelial migration; sJAM-C=soluble JAM-C; TNF=tumor necrosis factor; TLR=Toll-like receptor