Download vascular cell adhesion molecules

Adhesion Molecules
 Concept
 Naming
 Roles
 Classification
Concept

Cell adhesion molecules (CAMs):
proteins which exist in cell surface
involve in the binding of cells to each
other or to extracellular matrix.
Exist as couples( receptor-ligand)
 Co-effect with many couples

TCR complex,
Co –receptor,
Co-stimulator receptor, immunological synapse
B cell
Th cell
Th cell
Ag processing
B cell
activation
Interactions between B cell and Th cell
activation
Naming
Functions：
ICAM-1 (intercellular adhesion molecules),
LFA-1 (lymphocyte function – associated
antigen-1)
VCAM (vascular cell adhesion molecules),
PECAM1(platelet-endothelial-cell adhesion
molecule),


CD
CD58, CD152



Leukocyte differentiation antigen: Cell surface
molecules expressed (or disappeared) on
different developmental and differential phases
of blood cells .
CD: cluster of differentiation (uses of McAb)
CD molecules: The same differentiation antigen
recognized by different monoclone antibodies
from different labs is called CD molecule.
Naming by method of identification
CD molecules have a variety of functions
Classification
Most of the CAMs can be grouped by structure
into five families:
 Immunoglobulin (Ig) superfamily
 Integrin family
 Selectin family
 Cadherin family
 Mucin-like family
Others
Ig superfamily CAMs


The structure of these adhesion molecules
resemble that of Ig.
Members of the Ig superfamily include the
intercellular adhesion molecules (ICAMs),
vascular cell adhesion molecule (VCAM-1),
platelet-endothelial-cell adhesion molecule
(PECAM-1), and neural cell adhesion
molecule (NCAM).
Back
Integrins
Integrins consist of alpha(1-16) and beta(1 - 8)
chains
VLA-4 (very late antigen-4)（α4β1）------VCAM-1,
LFA-1 （α1β2）-----ICAM-1, ICAM-2, ICAM-3
举例：LFA-1（lymphocyte function associated
antigen-1)
 分布：thymocyte, T cell, macrophage
 配体：ICAM-1、2、3（表达于APC、内皮细胞）
Selectins
The molecule consists of one peptide chain
which has carbohydrate-binding domain.
 Bing
to
Sialyl-Lewis
(sialyl
Louis)
oligosaccharides
 three family members: endothelial (E)-selectin,
leukocyte (L)-selectin, and platelet (P)-selectin.
Roles— functions of cell adhesion
molecules
To mediate the contact and adhesion between
cell and cell, or between cell and extracellular
matrix resulting to various biologic effects.
Cell surface adhesion molecules play vital
roles in numerous cellular processes.
1 Involvement in lymphocyte formation and
differentiation
2 Involvement in immune response and immune
regulation
3 Involvement in inflammation
4 Involvement in lymphocyte homing
5 Involvement in regulation of apoptosis
1 Involvement in lymphocyte formation and
differentiation
Thymocyte Epithelial cell
CD2---------------IFA-3
IFA-1-------------- ICAM-1
2 Involvement in immune response and
immune regulation
Take part in recognition of immnocytes
3 Involvement in inflammation ·
mediate the adhesion of leukocytes with endothelial
cells during inflammation.
Transendothelial migration of leukocytes
Transendothelial migration demonstrates cooperativity
between leukocyte and endothelial cell adhesion molecules.
(1) rolling,
Initial rolling is mediated by binding of E-selectin molecules
on the vascular endothelium to sialylated carbohydrate
moieties on mucinlike CAMs.
(2) activation by chemoattractant stimulus,
A chemokine such as IL-8 then binds to its receptor on the
neutrophil, triggering an activating signal. This signal
induces a conformational change in the integrin
molecules, enabling them to adhere firmly to Igsuperfamily molecules on the endothelium
(3) arrest and adhesion,
The interaction between integrins and Ig-superfamily CAMs
stabilizes adhesion of the neutrophil to the endothelial
cell, enabling the cell to adhere firmly to the endothelial
cell.
(4) transendothelial migration
Transmigration of the leukocyte through adjacent
endothelial cells in a process called diapedesis. PECAM-1
is a crucial player in this step.
This step is largely unknown.
4 Involvement in lymphocyte homing ·
take part in lymphocyte homing and
recirculation
Homing receptor on lymphocyte:
L-selectin, LFA-1,
vascular addressin on HEVs:
GlyCAM-1(glycosylation dependent cell
adhesion molecules), CD34; ICAM-1
L-selectin ----- GlyCAM-1, CD34
LFA-1 ----- ICAM-1
淋巴细胞定向迁移，分布于淋巴器官和组织的不同部位
•High
endothelial
venule，HEV
（高内皮毛
细血管后微
静脉）
HEV are specialized venules found in lymphoid
tissues. Lymphocytes migrate from blood into
lymphoid tissues by attaching to and migrating
across the high endothelial cells of the vessels.
Clinical application of CD
and adhesion molecules
Elucidating pathological mechanism of
disease
 Application during diagonosis of disease
 Application during prevention and
treatment of disease
