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- Title
The podoplanin-CLEC-2 axis inhibits inflammation in sepsis.
- Authors
Rayes, Julie; Lax, Siân; Wichaiyo, Surasak; Watson, Stephanie K.; Ying Di; Lombard, Stephanie; Grygielska, Beata; Smith, Stuart W.; Skordilis, Kassiani; Watson, Steve P.
- 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-intraperitoneal 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 antiinflammatory axis regulating immune cell recruitment and activation in sepsis.
- Subjects
SEPSIS; GLYCOCALYX; INFLAMMATION; FIBRIN tissue adhesive; BLOOD platelets; PERITONEUM
- Publication
Nature Communications, 2017, Vol 8, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-017-02402-6