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An increasing body of evidence suggests that the immune system actively participates in the initiation, progression and persistence of atherosclerosis. Much conjecture exists about how monocytes are recruited specifically to the sites of perturbed flow. Here we study the influence of shear stress on the adhesion between immune cells and the endothelium.
|LIFEACT-mCherry T cell interacting with an anti-CD3+ anti-CD18 coated bead on the Biomembrane Force Probe |
A T cell is held by a micropipette on the left hand side. A biomembrane force probe consists in a bead adhering to a red blood cell, which is maintained by a micropipette (on the right hand side) with a controlled aspiration pressure that sets the red blood cell stiffness. The T cell emits a protrusion towards the antibody coated bead and exerts mechanical forces on it. The LIFEACT-mCherry fluorescently marks polymerized actin.
DIC microscopy (left), and mCherry channel (right). Frames are taken every 4 s. Movie is played at 10 frames per second. Bar is 5µm.
Video credit: Husson J, Chemin K, Bohineust A, Hivroz C, Henry N (2011) Force Generation upon T Cell Receptor Engagement. PLoS ONE 6(5): e19680. doi:10.1371/journal.pone.0019680
Vascular endothelial cells are known to respond to mechanical stress induced by blood flow. One type response is an increased expression of several leukocyte (i.e. white blood cells) adhesion molecules. Selectins appear to be primarily responsible for the initial capture of immune cells from the flowing blood. An increasing body of evidence suggests that the immune system actively participates in the initiation, progression and persistence of atherosclerosis. For instance, absence of P-selectin results in decreased fatty streaks, an early stage of atheroschlerotic lesions. Much conjecture exists about how monocytes are recruited specifically to the sites of perturbed flow. Turbulent or oscillatory flow may favor their recruitment.
Our research will focus on the influence of shear stress on the adhesion between immune cells and an endothelial cell monolayer, in order to decipher the relative contribution of the shear rate itself and of EC modifications. To do so we will use microfluidics and micropipette techniques, the later being a powerful tool to assess mechanical properties at the single-cell level.
See Julien Husson's earlier publications.