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Role of platelet Toll-like receptor signaling in hemostasis and inflammation.

Prof T. van der Poll

Duration:

Name researcher:

4 years

Amount granted:

€293.300

Year:

2013

Project number:

1309

Project leader:

Prof Tom van der Poll, Center for Experimental and Molecular Medicine (CEMM), AMC, Amsterdam
PhD student: Dorith (T.A.M.) Claushuis (May 2014 – May 2018)

About the project

The present project has addressed the role of platelets in sepsis.
Sepsis is a dysregulated host response to an infection. During infection (with e.g. bacteria), the immune system responds to combat the infection. When this response is dysregulated, the activated immune system, clotting and blood platelets can induce damage of the organs. Platelets are cells in the blood that are responsible for stopping bleeding when a blood vessel is damaged, by formation of a clot. We have shown that platelets can also influence the immune system during sepsis. Platelets can recruit immune cells to the site of the infection, can potentiate the function of immune cells and can trap bacteria. In detail, we have found that when platelets are reduced or absent, both mice and patients with sepsis have increased risk of dying and are more severely ill. Moreover, the host response is more severely dysregulated and vascular integrity is impaired with increased risk of bleeding when platelets are reduced or absent. We have shown that several receptors on the platelet surface and several platelets granules are involved in this protective role. Platelet receptors P-selectin and GPVI and indirectly platelet dense granules are necessary for the immune system to combat bacteria adequately. Alpha granules, signaling protein Btk en possibly GPVI are necessary to prevent bleeding during sepsis. Toll-like receptors on platelets do not play a crucial role in host defense or bleeding during sepsis. In conclusion, platelets contribute to adequate host defense and vascular integrity during sepsis.

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