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Emigration
of leukocytes:
The adhesion of leukocytes to the endothelial cell lining
of blood vessels and the subsequent migration of the leukocytes through
the vascular endothelium is an essential requirement for the successful
development of an inflammatory response.
Leukocytes in circulation patrol the endothelial cells
lining the blood vessels by leaving the central fast flowing stream of
blood flow and coming in close contact with the endothelial cell lining
in a process called "margination".
At the onset of an inflammatory stimulus, there is local
vasodilation and slowing in the velocity of blood flow in the local area.
This allows leukocytes to come in closer contact with the endothelial
lining. Endothelial cells exposed to an inflammatory stimulus rapidly
up-regulate the expression of P-selectin on their surface. Leukocytes have
on their surface glycoproteins that recognize and bind to P-selectin.
This produces a weak but important bond between the leukocytes and endothelial
cells. The leukocytes slowly "roll" across the endothelial surface
via this interaction - "rolling".
If the inflammatory stimulus is sufficient, endothelial
cells will be triggered to release inflammatory mediators such as PAF
and IL-8 which cause activation of the rolling leukocytes. In the case
of neutrophils, PAF/IL-8 stimulation triggers up-regulation of the surface
expression of beta2-integrins. Endothelial cells are simultaneously triggered
to up-regulate the amount of ICAM (intercellular adhesion molecule) expression
on their surface. The integrins bind to the ICAM causing firm "adhesion
(pavementing)" between the leukocyte and endothelial cell.
The leukocyte is the able to crawl to the boundary between
two adjacent endothelial cells. At the endothelial cell junctions there
is high concentrations of the adhesion molecule CD31. Activated leukocytes
also express CD31. CD31 is able to bind to itself and this CD31:CD31 interaction
between the leukocyte and the endothelial cell junction is the trigger
for "transmigration". During this process of transmigration,
the emigrating leukocyte secretes proteinases in order to digest a hole
in the basement membrane through which it squeezes to enter the perivascular
tissue.
 
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