Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 539

Adherent cell motion between the point of tight adhesion and the junction
between endothelial cells requires synergistic actions of α L β 2 -and α M β 2 -integrin

with ICAM1 and ICAM2, respectively, and possibly of β 1 integrin with VCAM.

Neutrophils express α M -integrin and slighly α 2 β 1 -integrin. Lymphocytes express

α L -and α 1 β 1 -integrin [ 979 ].

Leukocyte crawling can cause transient weakening of endothelial cell junctions
and formation of intracellular pores for para- and transcellular migration.
Intercellular adhesion molecule ICAM1 clustering stimulates protein Tyr kinases
to alter the function of vascular endothelial cell (VE)-cadherin (or Cdh5) [ 980 ].
Moreover, Cdh5-stabilizing Tyr phosphatase PTPRb (or VEPTP) dissociates

from VE-cadherin. Subsequently, γ -catenin is phosphorylated to further reduce

endothelial integrity.
Amine oxidase copper-containing AOC3, 105 expressed at the cell surface of
endothelial cells, regulates leukocyte migration. 106
Platelet endothelial cell adhesion molecule PECAM1 is recruited to sites of
transmigration from the lateral border recycling compartment (LBRC) using
microtubules and kinesin. Other adhesion molecules, such as T-cell surface
glycoprotein-E2 as well as junctional adhesion molecules JAM1 and JAM3, are also
enrolled [ 980 ].
The cell squeezes to penetrate the cell junction and cross the basement membrane
using platelet-endothelial cell adhesion molecule-1 (PECAM1) and endothelial
junctional adhesion molecules (JAM).
The transmigration takes 15 to 45 mn. Once leukocytes have ended their
transendothelial migration, they interact with chemokines presented by heparan
sulfate proteoglycans (perlecan, agrin, and collagen-18) in the basement membrane.
Leukocytes secrete various peptidases, such as matrix metallopeptidases and
heparanase. The degradation of the basement membrane results from a collaboration
among endothelial cells, leukocytes, and platelets, as these 3 types of cells produce
heparanase. Moreover, heparanase releases growth factors bound to basement
membrane proteoglycans. These growth factors contribute to angiogenesis and
tissue remodeling.
Once stably arrested by their integrin ligands on the TNF -activated vascular

endothelium, leukocytes most often undergo a cytoskeletal remodeling to move to
the cleft between endothelial cells, resisting detachment from the vessel wall by the
blood flow, before crossing the endothelium.
Activated ligand-bound G

α

α i -coupled receptors are required in adhesion and
rolling of leukocytes on the wetted surface of the endothelium in response to
chemokine gradients. 107 α 4 -integrin-

VCAM1-dependent firm adhesion of lymphocytes on endothelial cells do not

However, VCAM1 expression level and

105 A.k.a. vascular adhesion protein-1 (VAP1).
106 In AOC3-deficient mice, rolling velocity of polynuclear leukocytes and lymphocytes on the
endothelium in inflammation sites is greater than in wild-type mice [ 985 ].
107 G-protein subunits G

α i3 are expressed in granulocytes, lymphocytes, and
airway smooth muscle, epithelial, and vascular endothelial cells.

α i1 ,G α i2 ,andG