The podoplanin-CLEC-2 axis inhibits inflammation in sepsis

Research output: Contribution to journalArticle

Authors

  • Surasak Wichaiyo
  • Stephanie Watson
  • Ying Di
  • Stephanie Lombard
  • Beata Grygielska
  • Kassiani Skordilis

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 perivascular 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.

Details

Original languageEnglish
Article number2239
JournalNature Communications
Volume8
Early online date21 Dec 2017
Publication statusPublished - 21 Dec 2017