| First Author | Corken A | Year | 2014 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 34 |
| Issue | 5 | Pages | 996-1001 |
| PubMed ID | 24504734 | Mgi Jnum | J:309924 |
| Mgi Id | MGI:6708481 | Doi | 10.1161/ATVBAHA.113.303113 |
| Citation | Corken A, et al. (2014) Platelet glycoprotein Ib-IX as a regulator of systemic inflammation. Arterioscler Thromb Vasc Biol 34(5):996-1001 |
| abstractText | 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-alpha 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. |
