Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 535

9.7.3 Integrin-Based Cell Adhesion

The adhesive potential of a cell is defined by its repertoire of integrins that serve
as adhesion receptors (Vol. 1 - Chap. 7. Plasma Membrane). These transmembrane
proteins mediate adhesion of both resting and migrating cells. Coupling between
actin and integrins serves as a hook for migrating cells.
Cell displacement is achieved partly through construction and reconstruction of
adhesion foci. Moreover, migrating cells in the extracellular matrix remain bound
to matrix constituents in preferential routes (haptokinesis and -taxis). Whereas
mesenchymal cells are confined to matrix tracks, leukocytes prioritize guidance
signals. They move along a chemoattractant gradient.

9.7.4 Intracellular Signaling in Endothelial Cells

Cytokines activate endothelial cells that then express adhesion molecules at their
wetted surface such as vascular cell adhesion molecule VCAM1 to regulate
leukocyte transmigration to sites of inflammation. In normal conditions, adhesion
molecules are not produced. In particular, endothelial cells express microRNA-126
that inhibits VCAM1 expression [ 981 ].
The endothelium can either favor or inhibit flowing cell adhesion on its wetted
surface. Released nitric oxide can inhibit adhesion of cells involved in inflammation
or coagulation. In addition, endothelial cells continually produce 13-hydroxy-
octadecadienoic acid (13HODE) that confers to normal endothelium resistance to
platelet or monocyte adherence.
Conversely, adhesion molecules attract leukocytes for transmigration. Numerous
adhesion molecules localize at junctions between adjacent endothelial cells to
support leukocyte diapedesis, such as platelet endothelial cell adhesion molecule
PECAM1, ICAM2, junctional adhesion molecules (JAM1-JAM3), T-cell sur-
face glycoprotein-E2 (or CD99), and endothelial cell-selective adhesion molecule
(ESAM) [ 980 ]. Some of these molecules are involved in the extravasation of specific
leukocyte types or in response to specific stimuli.
E-selectin and intercellular adhesion molecule ICAM1 lodge also in focal
adhesions, i.e., filamentous actin-linked integrin clusters that mediate cell-matrix
adhesion [ 980 ]. Proteins that reside at both docking sites and focal adhesions include
α -actinin, filamin, paxillin, and vinculin, as well as focal adhesion kinase.

Actin crosslinkers control connections between the plasma membrane and
intracellular signaling machinery. Filamin binds small guanosine triphosphatases
Rho and Ral, their activators such as RhoGEF Trio, and caveolin-1 to promote
localized signal transduction [ 980 ].
In response to leukocyte binding, clusters of E-selectin and integrin ligands
on the endothelial surface augment the intracytosolic concentration of Ca 2 + in