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

Platelet glycoprotein Ib-IX as a regulator of systemic inflammation.

Author information

1
From the Departments of Physiology and Biophysics (A.C., S.R., J.D., J.W.) and Pathology (S.R.P.), University of Arkansas for Medical Sciences, Little Rock.

Abstract

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

Comment in

PMID:
24504734
PMCID:
PMC3991762
DOI:
10.1161/ATVBAHA.113.303113
[Indexed for MEDLINE]
Free PMC Article
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