The podoplanin-CLEC-2 axis inhibits inflammation in sepsis.

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.

• Authors: Julie Rayes, Siân Lax, Surasak Wichaiyo, Stephanie K Watson, Ying Di, Stephanie Lombard, Beata Grygielska, Stuart W Smith, Kassiani Skordilis, Steve P Watson
• Journal: Nature communications (Nat Commun) Vol. 8 Issue 1 Pg. 2239 (12 21 2017) ISSN: 2041-1723 [Electronic] England
• PMID: 29269852 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CLEC-2 protein, mouse
• Chemokines
• Cytokines
• Gp38 protein, mouse
• Lectins, C-Type
• Lipopolysaccharides
• Membrane Glycoproteins
• Platelet Membrane Glycoproteins
• platelet membrane glycoprotein VI

Topics

• Animals
• Blood Platelets (immunology)
• Cecum (surgery)
• Chemokines (immunology)
• Cytokines (immunology)
• Inflammation (immunology)
• Injections, Intraperitoneal
• Kidney (immunology, pathology)
• Lectins, C-Type (genetics, immunology)
• Ligation
• Lipopolysaccharides (toxicity)
• Macrophages (immunology)
• Membrane Glycoproteins (genetics, immunology)
• Mice
• Multiple Organ Failure (immunology)
• Phagocytosis (immunology)
• Platelet Membrane Glycoproteins (genetics, immunology)
• Punctures
• Sepsis (chemically induced, immunology)