Adhesion molecule play a major role
in our biological activity, from
hematopoiesis until apoptosis, many
types of it and different mechanisms
but they contribute together in a
harmonic system. A good example is
extavasation of neutrophil or
leukocytes general
ADHESION
MOLECULES
Ali mohamed
Prof. Dr. Salma Y.
AboElNazar
Adhesion molcules are: cell surface proteins that mediate the interaction between
cells, or between cells and the extracellular matrix (Burbach, 2021)
If the adhesion was between cell-cell it call CAM and if it was between cell-
subsrtatum ti called SAM. (Golias et al., 2011)
immunoglobulin-like adhesion molecules, integrins, cadherins and selectins (Ren
et al., 2011)
Note: lose of cell-cell interaction could cause cancer (Wardhan & Mudgal, 2018)
- Selectins
are a diverse group of calcium-dependent, type I transmembrane molecules
(Ghosh, 2020)
It have a major role in many biological process like: extravasation, inflammation,
hemostasis and tumor expression and others,
Selectin have three famous types: P-selectin, E-selectin which are found on
endothelial cell and L-selectin which are found on leukocyte
Selectin binds to carbohydrate by recognizing that antigen sialyl-Lewisx (sLex)
antigen (Golias et al., 2011) Selectin have N-terminal an C-lactin domain, EGF-
like domain, CRP and short cytoplasmic tail. (Tedder et al., 1995) (Golias et al.,
2011)
P-selectin E-selectin L-selectin
Found in platelets and Found on epithelial cell Found on leukocytes
endothelial cells
Mobilized by Found in hypersensitivity
inflammation agent like sites and in heart rejected
thrombin and histamine
Play role in extravasation Play role in leukocyte Play role in adhesion to
homing EV
Bind to PSGL in Found as active form in
extravasation serum
- Integrins
Are the most protein in cell-cell interaction, composed two ligands (α and β) bind
by disulfide bonds At least there are 15 types of α and in some books there is 25
types and 9 types of β. (Alberts, 2002) (Golias et al., 2011) example of integrin is:
LFA-1
Integrins mediating interactions between cytoskeleton and extracellular matrix
cytoplasmic tail β subunit binds to anchor proteins which bind directly to actin or to
another anchor, this linkage cause clustering of the integrins which from focal
adhesions. (Alberts, 2002) integrins need inside signal from cell to get out of the
surface so cell could control of integrins and integrins control of cell.. (Alberts, 2002)
- Cadherins:
plays paramount roles in organ development, functions as a peptide transporter and
cell adhesion molecules. (Lee et al., 2010) it have six subfamilies include: E-
cadherin which is expressed in epithelia, N-cadherin which is expressed in neural
and mesenchymal, and VE-cadherin which is present in vascular endothelia
(Ratheesh & Yap, 2012). It thought that cadherin play a role in cancer progression.
Β-catenin, α-catenin and p120 catenin represent the core of cadherin (Ratheesh &
Yap, 2012).
- Mucins:
repeat sequences rich in serine, threonine, and proline residues that are heavily O-
glycosylated (van Putten & Strijbis, 2017) it is not only receptors but also sensors
(Hollingsworth & Swanson, 2004), mucin transmembrane after binding to bacteria
or other stimuli, activate phosphorylation which initiate inflammatory response, EC
adhesion, apoptosis. (van Putten & Strijbis, 2017) Mucin also play role in secretion
HCL from gastric (Hollingsworth & Swanson, 2004) mucin over expression is a
marker for cancer (van Putten & Strijbis, 2017) (Hollingsworth & Swanson, 2004)
mucin transmembrane have 3 domains: Sea urchin sperm protein. Enterokinase,
and agrin domain. Which know by SEA domain.
There is a relation between mucin and P-selectin and L-selectin (Wahrenbrock et
al., 2003)
- Immunoglobulin superfamily
is a protein domain that is similar in amino acid sequence and structure to the Ig
domains of immunoglobulins (Horstkorte & Fuss, 2012) it similar to
immunoglobulin with β sheets and V region and C region. Example: CD 4 and
CD8
At adhesion molecules it known by ICAM it have isoforms which different in size
and conformation so it divided to two sub groups:
1- proteins with one or more Ig-like domain(s)
2- proteins with Ig-like domains and additional fibronectin type III repeats
Horstkorte & Fuss, 2012)
the most important ligand for ICAM is: β2 integrins LFA-1 and Mac1 (Golias et
al., 2011)
- Case study: Neutrophil extravasation it have 5 steps:
1- Tethering: at inflammation state P-selectin and E-selctin on endothelial cell is
increase which bond to PSGL-1 so neutrophil get slower to 5 um/s this case
called slow rolling (Futosi et al., 2013) (Kolaczkowska & Kubes, 2013)
2- Rolling: is made by bonds between surface molcules and neutrophil molecule,
the major molecule is selevtin and selectin family (Cugno et al., 2021) L-
selectin on neutrophil while rolling facilitate their secondry tethering
3- adhesion: he dissociation of a P-selectin–PSGL1 bond at the rear of the cell
should be balanced with the formation of another bond at the leading edge
(Kolaczkowska & Kubes, 2013)
CXCL8 signal via CXCR2 to activate neutrophils (Kolaczkowska & Kubes, 2013)
Neutrophil have heparan sulphate with negative charge which bond to chemokines
with positive charge, then activate G- coupeled protein which expressed integrins
that bind to ICAM receptors
4- Crawling: neutrophils cross several barriers consisting of: endothelium,
basement membrane and pericytes.
1- To cross endothelium via interaction between MAC1 and IMAC 1 then
partially digest basement membrane so it prefers to cross via low extracellular
matrix.
2- To migrate through pericytes, by interaction between ICAM-1 and MAC1
5- Transmigration: Transmigration requires integrins and CAMs (ICAM1,
ICAM2 and vascular cell adhesion protein 1 (VCAM1)) and other adhesion
molecules, ectoenzymes and others.
Transmigration have two methods: 1- paracellularly 2- transcellularly.
Paracellularly means: between endothelial and transcellularly means through
endothelial
NOTE: not all neutrophil recruitment requires selectins and/or integrins, as like
Neutrophils lacking selectin ligands and integrins still adhere to blood vessels in the
lungs (Kolaczkowska & Kubes, 2013)
- References
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