Rullo et al. describe how actin polymerization helps leukocytes maintain their attachments to blood vessel walls.

A key step during the recruitment of white blood cells into inflamed tissues is chemokine-triggered activation of integrins, such as VLA-4, that attach leukocytes to the endothelial cells lining the blood vessel. These adhesions are quickly stabilized to prevent the leukocytes from being swept away in the flow of blood. Rullo et al. treated monocytes with inhibitors of actin polymerization and found that, although the drugs had no effect on the activation of VLA-4’s affinity for its ligand VCAM-1, they reduced the cells’ ability to form flow-resistant adhesions in vitro.

Monocytes exposed to fluid flow quickly formed actin-rich upstream structures, which contained VLA-4 and kept the cells anchored to VCAM-1. But when actin polymerization was blocked, these anchors became longer and more fragile, stretching out behind the leukocytes as they detached from the surface. The accumulation of actin within the leukocyte anchors was dependent on the small GTPases Rap1 and Rac, as well as on activation of the lipid kinase PI3K. Inhibiting any of these proteins blocked actin polymerization and reduced stable leukocyte attachment.

Rap1 and PI3K can both be activated by mechanical stress, suggesting that these two proteins sense when leukocyte adhesions are under tension and trigger a rapid reinforcement of the cell's attachments. The authors now want to investigate whether integrin-based signaling pathways contribute to tension sensing and to examine the role of myosin in stabilizing leukocyte adhesions.

et al
J. Cell Biol.