Platelet glycoprotein Ib-IX as a regulator of systemic inflammation

Arterioscler Thromb Vasc Biol. 2014 May;34(5):996-1001. doi: 10.1161/ATVBAHA.113.303113. Epub 2014 Feb 6.


Objective: The platelet glycoprotein Ib-IX (GP Ib-IX) receptor is a well-characterized adhesion receptor supporting hemostasis and thrombosis via interactions with von Willebrand factor. We examine the GP Ib-IX/von Willebrand factor axis in murine polymicrobial sepsis, as modeled by cecal ligation and puncture (CLP).

Approach and results: Genetic absence of the GP Ib-IX ligand, von Willebrand factor, prolongs survival after CLP, but absence of the receptor, GP Ib-IX, does not. Because absence of either von Willebrand factor or GP Ib-IX significantly impairs hemostasis and thrombosis, we sought to define additional GP Ib-IX-dependent pathways impacting survival in the CLP model. We document that the absence of GP Ib-IX leads to reduced platelet-neutrophil and platelet-monocyte interactions. Twenty-four hours after CLP, absence of GP Ib-IX coincides with an alteration in cytokine levels, such as tumor necrosis factor-α secreted by monocytes, and increased macrophage-1 antigen expression by neutrophils.

Conclusions: In contrast to the well-characterized proinflammatory properties of platelets, we describe in the CLP model an anti-inflammatory property associated with platelet GP Ib-IX. Thus, a single platelet receptor displays a dual modulatory role in both the thrombotic and inflammatory pathways associated with polymicrobial sepsis. In sharing leucine-rich motifs with toll-like receptors, platelet GP Ib-IX can be considered a multifunctional participant in hemostasis, thrombosis, and the inflammatory cascade. The results highlight a dynamic role for platelets in systemic inflammation and add to the complex pathophysiologic events that occur during the dysregulated coagulation and inflammation associated with sepsis.

Keywords: cytokines; monocytes; neutrophils; platelet glycoprotein GPIb-IX complex; sepsis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Platelets / immunology
  • Blood Platelets / metabolism*
  • Cecum / microbiology
  • Cecum / surgery
  • Cell Communication
  • Disease Models, Animal
  • Hemostasis
  • Humans
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism
  • Ligands
  • Ligation
  • Macrophage-1 Antigen / blood
  • Male
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Monocytes / metabolism
  • Neutrophils / metabolism
  • Platelet Glycoprotein GPIb-IX Complex / genetics
  • Platelet Glycoprotein GPIb-IX Complex / metabolism*
  • Sepsis / blood
  • Sepsis / genetics
  • Sepsis / immunology
  • Sepsis / metabolism*
  • Sepsis / microbiology
  • Signal Transduction
  • Thrombosis / blood
  • Thrombosis / metabolism
  • Time Factors
  • Tumor Necrosis Factor-alpha / blood
  • von Willebrand Factor / genetics
  • von Willebrand Factor / metabolism


  • IL4 protein, human
  • Ligands
  • Macrophage-1 Antigen
  • Platelet Glycoprotein GPIb-IX Complex
  • Tumor Necrosis Factor-alpha
  • adhesion receptor
  • von Willebrand Factor
  • Interleukin-4