Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 540

depend on G α i2 in the vascular endothelium favors the

diapedesis of firmly adherent lymphocytes [ 987 ]. Chemokine-stimulated G-protein-
coupled receptors and their effectors, especially CDC42, RhoA, Rac, and Rap
GTPases, promote actin reorganization.
In lymphocytes, Rac GTPase activation by integrins and chemokines depends
on dedicator of cytokinesis (DOCK). T lymphocytes use 2 different chemokine-
triggered actin processes [ 988 ]: (1) DOCK-dependent mechanism to move lat-
erally along the endothelium and (2) DOCK-independent procedure to cross the
endothelium.

α i signaling. Subunit G

9.7.7 Extravasation Modes

Leukocytes use both para- and transcellular extravasations. Paracellular diapedesis
requires a transient loss of cadherin-5 that determines contact between apposed
endothelial cells. Cadherin-5 is regulated by adaptor catenins that mediate inter-
actions between cadherin-5 and the cortical actin cytoskeleton. Loss of cadherin-5
function results from a combination of stress fiber contraction by activated RhoA
and phosphorylation of cadherin-5 and catenins. Cadherin-5 to which PTPRb
phosphatase dissociates, is phosphorylated by Src and FAK2 kinases.
Transcellular diapedesis is associated with an endothelial transmigratory
structure composed of docking microvilli that surrounds and guides migrating
leukocytes (Sect. 11.5.1 ). This villus-like structure is constituted of intercellular
adhesion molecules, particularly leukocyte integrins and endothelial IgCAMs [ 989 ].
Both B and T lymphocytes preferentially use the transcellular route.
Vesiculovacuolar organelles contribute to the lateral border recycling
compartment for the transport of adhesion molecules such as PECAM1 to sites
of transmigration [ 980 ]. Transcellular migration may require endothelial caveolin-1
for the formation of transcellular pores used by migrating cells.
Intermediate filament networks of both lymphocytes and endothelial cells
contribute to lymphocyte migration. Intermediate filaments are implicated in the
distribution of adhesion molecules, such as ICAM1 and VCAM1 on endothelial
cells and

α V β 1 -integrin on lymphocytes. Intermediate filaments of both endothelial
cells and lymphocytes form a dynamic anchoring structure at the between-cell
contact loci. The initiation of this anchoring structure requires vimentin [ 990 ].
Vimentin in both the endothelial cell and lymphocyte stabilizes endothelial cell-
lymphocyte interactions and reorganizes the intermediate filament network.
Leukocyte extravasation requires not only cell adhesion molecules and chemoat-
tractants, but also plasmalemmal enzymatic reactions on both leukocytes and
endothelial cells. Ectoenzymes (nucleotidases, cyclases, ADP ribosyltransferases,
peptidases, and oxidases) that have catalytic domains outside the plasma membrane,
regulate the cell recruitment [ 991 ].
Ectonucleotidases, such as ectonucleoside triphosphate diphosphohydrolase
ENTPD1 5 -nucleotidase, and and adenosine deaminase regulate ATP and