Neutrophil DREAM promotes neutrophil recruitment in vascular inflammation.
J Exp Med
; 219(1)2022 01 03.
Article
em En
| MEDLINE
| ID: mdl-34751735
ABSTRACT
The interaction between neutrophils and endothelial cells is critical for the pathogenesis of vascular inflammation. However, the regulation of neutrophil adhesive function remains not fully understood. Intravital microscopy demonstrates that neutrophil DREAM promotes neutrophil recruitment to sites of inflammation induced by TNF-α but not MIP-2 or fMLP. We observe that neutrophil DREAM represses expression of A20, a negative regulator of NF-κB activity, and enhances expression of pro-inflammatory molecules and phosphorylation of IκB kinase (IKK) after TNF-α stimulation. Studies using genetic and pharmacologic approaches reveal that DREAM deficiency and IKKß inhibition significantly diminish the ligand-binding activity of ß2 integrins in TNF-α-stimulated neutrophils or neutrophil-like HL-60 cells. Neutrophil DREAM promotes degranulation through IKKß-mediated SNAP-23 phosphorylation. Using sickle cell disease mice lacking DREAM, we show that hematopoietic DREAM promotes vaso-occlusive events in microvessels following TNF-α challenge. Our study provides evidence that targeting DREAM might be a novel therapeutic strategy to reduce excessive neutrophil recruitment in inflammatory diseases.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
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Infiltração de Neutrófilos
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Proteínas Interatuantes com Canais de Kv
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Microvasos
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Inflamação
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Neutrófilos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article