Biomedical Engineering Reference
In-Depth Information
Table 11.6.
Adhesion molecules involved in leukocyte migration across blood vessel wall during
inflammation (Source: [
1447
,
1448
]; GAGCAM: glycosaminoglycan cell adhesion molecule, or
glycosylation-dependent CAM [GlyCAM1]); ICAM: intercellular adhesion molecule; MAdCAM:
mucosal vascular addressin cell adhesion molecule; PECAM: platelet endothelial cell adhesion
molecule; VCAM: vascular cell adhesion molecule). 3-fucosyl
N
acetyl lactosamine (FAL; a.k.a.
Lewis X or CD15) is a glucid adhesion molecule expressed on glycoproteins and -lipids as well as
proteoglycans that is synthezised by fucosyltransferases FuT4 and FuT9. It mediates neutrophil
chemotaxis and phagocytosis. The random contact is followed by rolling to a stop involving
selectins. Sticking and extravasation require integrins.
Extravasation step
Adhesion molecules
Rolling
Selectins (CD62E/L/P), FAL (CD15), PSGL1 (CD162)
GAGCAM1, neutrophil addressins
Stopping
α
4
β
1
-,
β
2
-,
α
4
β
7
-,
α
L
β
2
-integrins
ICAM1, VCAM1, MadCAM1
Transmigration
β
2
-integrins
ICAM1, VCAM1, PECAM1
molecules (e.g., ICAM1
and
ICAM2),
and
vascular
cell
adhesion molecule
VCAM1; (4) integrins, such as
α
M
β
2
-integrin; as well
as (5) integrin-associated protein, or leukocyte surface antigen CD47 (Table
11.6
;
Vols.1-Chap.7.PlasmaMembraneand2-Chap.6.CellMotility). Leukocyte
integrins connect to their endothelial ligands that are organized in tetraspanin-
enriched microdomains [
1445
]. These cellular structures mediate the contact
between leukocytes and endothelial cells during extravasation.
Endothelial adhesion receptors of activated endothelial cells localize to adhesion
platforms that are enriched in tetraspanins in apical microvilli. Tetraspanins interact
simultaneously with other tetraspanins and other types of transmembrane receptors.
These adhesion platforms contain selectins and members of the Ig superfamily
(VCAM1, ICAM1, ICAM2, PECAM1, and JAMs) [
1445
]. These functional units
that coalesce around adherent leukocytes are connected to the actin cytoskeleton
and contain
α
4
β
1
-,
α
4
β
7
-,
α
L
β
2
-, and
-actinin, ezrin, moesin, paxillin, talin, vinculin, and vasoactive
stimulatory phosphoprotein. They are regulated by the Rho-RoCK pathway and
PIP
2
second messengers. These docking structures, or transmigratory cups, stabilize
firm adhesion of leukocyte to endothelium, hence preventing leukocyte detachment.
During leukocyte displacement over the endothelium, L-selectin, epican (CD44),
ICAM1, and ICAM3, among others redistribute to the leukocyte rear pole. On the
oher hand, integrins, such as
α
α
M
β
2
-integrins, and chemokine receptors
localize to the leading edge and endothelial contact area.
32
Leukocytes probe for sites suitable for diapedesis by constructing protrusions.
When they find an appropriate site for migration, filopodia evolve into an invasive
pseudopod to cross the endothelium. During paracellular transmigration, ICAM1
α
L
β
2
-and
32
Leukocyte crawling relies on
α
β
2
-integrin in lymphocytes,
α
β
2
-
α
β
2
-integrins in mono-
L
L
M
cytes, and
α
β
2
-integrin in neutrophils [
1445
].
M
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