The podoplanin-CLEC-2 axis inhibits inflammation in sepsis.
Nat Commun
; 8(1): 2239, 2017 12 21.
Article
em En
| MEDLINE
| ID: mdl-29269852
ABSTRACT
Platelets play a critical role in vascular inflammation through the podoplanin and collagen/fibrin receptors, C-type-lectin-like-2 (CLEC-2) and glycoprotein VI (GPVI), respectively. Both receptors regulate endothelial permeability and prevent peri-vascular bleeding in inflammation. Here we show that platelet-specific deletion of CLEC-2 but not GPVI leads to enhanced systemic inflammation and accelerated organ injury in two mouse models of sepsis-intra-peritoneal lipopolysaccharide and cecal ligation and puncture. CLEC-2 deficiency is associated with reduced numbers of podoplanin-expressing macrophages despite increased cytokine and chemokine levels in the infected peritoneum. Pharmacological inhibition of the interaction between CLEC-2 and podoplanin regulates immune cell infiltration and the inflammatory reaction during sepsis, suggesting that activation of podoplanin underlies the anti-inflammatory action of platelet CLEC-2. We suggest podoplanin-CLEC-2 as a novel anti-inflammatory axis regulating immune cell recruitment and activation in sepsis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plaquetas
/
Glicoproteínas de Membrana
/
Sepse
/
Lectinas Tipo C
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Inflamação
/
Macrófagos
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Insuficiência de Múltiplos Órgãos
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article