Biomedical Engineering Reference
In-Depth Information
7.7 CELL TRANSFER DURING INFLAMMATION/WHITE BLOOD
CELL ROLLING AND STICKING
One of the most important properties of the endothelium is to allow white blood cells
to pass through the endothelial cell wall during inflammatory conditions. From our previ-
ous discussion, we have stated that white blood cells, although there are many different
types of these cells, are all involved in the removal and/or elimination of foreign particles.
This task could not be accomplished if the white blood cells are segregated within the cir-
culatory system because foreign particles can propagate anywhere within the body. One
of the earliest responses to an infection is the expression of adhesion molecules on the cap-
illary endothelial cell surface (e.g., E-selectin and various integrins). White blood cells can
bind to these receptors to make an initial contact with the endothelial cells. White blood
cells tend to roll along the capillary, making and breaking adhesions along the way. At
some point, the adhesion between the white blood cell and the endothelial cell wall
becomes more stable and the cell does not roll along the blood vessel anymore, and there-
fore it stays in one location. Once this stable adhesion occurs, it is possible for the white
blood cell to cross the endothelial cell barrier, in a process termed transmigration. Once
this occurs, the white blood cells migrate toward the site of infection along a chemotactic
gradient. Again, the initial attachment of white blood cells to the endothelial cell wall is
typically mediated through various selectin molecules. These adhesions are characterized
by rapid association and dissociation constants. After selectin binding, there is a reorgani-
zation of the white blood cell membrane bound integrins, which facilitate a more
stable adhesion (the kinetic constants are slower). As more selectins make contact with the
endothelial cells, the reorganization of integrins occurs much more rapidly.
Typically, the white blood cell selectin density changes depending on factors such as
shear stress, and presence of cytokines, among others. At a selectin density of less than
15 molecules/cm 2 , white blood cell adhesion is unstable, even at low fluid velocities. At
higher selectin densities, white blood cell adhesion is more stable but transient, and it is
likely that integrins will be redistributed to mediate stable adhesion. The force required to
break one selectin bond is on the order of 20 pN, and the bond typically acts over a dis-
tance of 0.5 angstroms. As the adhesion becomes stronger, from either more selectin bonds
or more integrin bonds, the white blood cell becomes stationary even though the largest
fluid shear forces are acting on the bound white blood cell (because the white blood cells
would be located along the blood vessel wall). The strength of an integrin adhesion has
been reported to be in the range of 50 pN. This process of tight adhesion normally occurs
within the venous side of capillaries or within post-capillary venules. At the point of
stable adhesion, the cytoskeleton of the white blood cell is reorganized so that the cell flat-
tens out over the endothelial cell wall. This reduces the face on exposure area to the fluid
velocity (thus minimizing the face-on pressure). Pseudopods from the leukocyte locate the
intercellular cleft between neighboring endothelial cells. Pseudopods typically express
many adhesion molecules. The white blood cell passes through the cleft primarily via the
action of PECAM (platelet endothelial cell adhesion molecule), which acts to pull the cell
through the gap. The strength of a PECAM bond can be as large as 1 to 10 nN. The leuko-
cytes then migrate through the basement membrane along a chemotactic gradient to reach
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