Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 534

Table 9.24. Leukocyte integrins involved at the beginning of transendothelial migration (CR:
complement receptor; ICAM: intercellular adhesion molecule; LFA: leukocyte function-associated
antigen; Mac1: macrophage-1 antigen; VCAM: vascular cell adhesion molecule; VLA: very-late-
activation antigen).

Integrin type Other alias Endothelial ligands

α 4 β 1 VLA4, CD29-CD49d ICAM1, VCAM1

α L β 2

LFA1, CD11a-CD18 ICAM1

α M β 2 Mac1, CR3, CD11b-CD18 ICAM1

Prior to leukocyte transendothelial migration, heterotypic intercellular junctions
are mediated by various types of adhesion molecules (Table 9.24 ; Vol. 1 - Chap. 7.
Plasma Membrane). Activation of endothelial cells by inflammatory cytokines, such
as tumor necrosis factor- and interleukin-1, increases the density of selectins and

integrin ligands, such as intercellular (ICAM1) and vascular (VCAM1) cell adhe-
sion molecule, on the luminal, apical surface. Clusters of adhesion molecules form
on aggregates of pre-existing plasmalemmal nanodomains that contain members of
the tetraspanin family, such as Tspan29 and Tspan24 as well as eventually Tspan28.
These clusters construct rings around bound leukocytes.
Clusters of integrin ligands recruit regulatory and structural elements such as
filamentous actin, thereby connecting to the cortical actin cytoskeleton. These
clusters can associate with protrusions of the apical endothelial membrane to
constitute docking sites that can even encapsulate adherent leukocytes.
Endothelial cell adhesion molecules are connected to actin-binding adaptors such

α

as -actinin, cortactin, and filamin. Hence, a diapedesis synapse results that forms

a strong intercellular adhesion and force-transduction platform to secure anchorage
of migrating leukocytes to the cortical cytoskeleton of endothelial cells.

α

9.7.2 Cell Movement over the Wetted Endothelial Surface

Flowing cells then undergo an extravasation with sequential steps, the kinetics of
which depends on shear. Leukocyte extravasation steps include [ 979 ]: (1) capture
and tethering on the inflamed endothelium; (2) rolling; (3) activation of leukocytes
by endothelium-bound chemokines; (4) arrest and firm adherence of activated
leukocytes to the endothelium; and finally (5) locomotion (crawling) over the
endothelial wetted surface; before they undergo diapedesis, or transendothelial
migration (TEM), that needs degradation of the subendothelial basement membrane
to continue motion through interstitium.
When cells are crawling on the wetted surface, they develop ventral membrane
protrusions on the vessel wall to probe for permissive sites on the endothelial
surface. In addition to podosomes and pseudopodia, chemokines and shear stress
elicit the formation of filopodia composed of parallel bundles of actin filaments
with actin-associated proteins [ 980 ].