The podoplanin-CLEC-2 axis inhibits inflammation in sepsis

Julie Rayes, Sian Lax, Surasak Wichaiyo, Stephanie Watson, Ying Di, Stephanie Lombard, Beata Grygielska, Stuart Smith, Kassiani Skordilis, Steve Watson

Research output: Contribution to journalArticlepeer-review

58 Citations (Scopus)
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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.
Original languageEnglish
Article number2239
JournalNature Communications
Volume8
Early online date21 Dec 2017
DOIs
Publication statusPublished - 21 Dec 2017

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