The podoplanin-CLEC-2 axis inhibits inflammation in sepsis

Julie Rayes (), Siân Lax, Surasak Wichaiyo, Stephanie K. Watson, Ying Di, Stephanie Lombard, Beata Grygielska, Stuart W. Smith, Kassiani Skordilis and Steve P. Watson
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Julie Rayes: University of Birmingham
Siân Lax: University of Birmingham
Surasak Wichaiyo: University of Birmingham
Stephanie K. Watson: University of Birmingham
Ying Di: University of Birmingham
Stephanie Lombard: University of Birmingham
Beata Grygielska: University of Birmingham
Stuart W. Smith: Hospital Birmingham
Kassiani Skordilis: Queen Elizabeth Hospital Birmingham
Steve P. Watson: University of Birmingham

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-02402-6

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