Inserm, Institut national de la santé et de la recherche médicale
Faculté de pharmacie, Aix Marseille Université

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Roles of platelets in inflammation

Grants from Actelion ltd.

This project is performed by Soraya Mezouar (PhD Student)

The traffic signals for neutrophil localization in inflammation have been described to function in a sequence of at least three steps, with multiple molecular choices at each step. This molecular model was described based on the observations that at sites of inflammation, leukocytes first roll to the vessel wall and then become firmly adherent at a single location on the vessel wall before diapedesis. Tethering brings leukocytes into proximity with chemoattractants present at sites of injury/inflammation.

Chemoattractants activate integrin that then could interact with its ligand and induces the firm adhesion of leucocytes at the site of injury. Using real-time digital intravital microscopy we recently establish a new method to track in real time the different cells involved in the inflammatory process.

Our results indicate a key role of circulation platelets. In the minutes following inflammation, platelets rolled and adhered at the surface of the inflamed endothelium. Adherent platelets interacted with circulating platelets and formed instable thrombi containing both platelets and leucocytes. Twenty to 30 minutes following the inflammation, leucocytes roll on adherent platelets expressing P-selectin. The interaction of platelets with the endothelium is abolished in vWF-/- mice. The formation of platelet rich thrombi is prevented by treatment with Clopidogrel. When platelets are absent or inactivated, the expression of P-selectin at the site of inflammation is significantly reduced thereby inhibiting the rolling of leucocytes.

Infusion of wild type platelets in P-selectin null mice partially restores the rolling, adhesion and transmigration of leucocytes. Altogether these results indicate that in the minutes following an inflammation platelets interact with the endothelial wall via vWF, are activated and expressed P-selectin. The platelet P-selectin plays an important role for the rolling of leucocytes leading to their transmigration.

Leucocyte extravasation following inflammation

Inflammation Neutrophils

Main collaborations on this topic : Dr Peter Lenting and Dr Cécile Denis, Inserm, Paris.