Biomedical Engineering Reference
In-Depth Information
activation under physiologic conditions. Moreover, failure of this regulatory
mechanism may underlie a chronic inflammatory state characteristic of a number of
pathological conditions associated with obesity.
4.1 The Shear Stress Environment of the Neutrophil
For Newtonian flow, shear stress applied to the cell surface or to a neighboring
fluid element is linearly proportional to shear rate, which is defined by the spatial
velocity gradient. Whereas the shear stress is related to the physical deformation-
inducing force per unit surface area acting on the cell surface, the shear rate
governs the macromolecular or cellular mass transport within the locale of the cell
[
93
]. Typically, both shear rates and shear stresses are reported at or in the
proximity of the blood vessel wall. Wall shear stresses are sometimes used as a
reference measure to give an indication of the fluid flow conditions in a particular
site of the circulation.
Generally, shear stress magnitudes vary over time and location along the vas-
culature. They can reach up to 50 dynes/cm
2
under normotensive conditions, but
more than 100 dynes/cm
2
under hypertensive conditions [
94
]. Moreover, while
shear stresses on the vascular wall are pulsatile in the arterial system, they become
steady in the microcirculation and in the venous system. Mean wall shear stresses
in large arteries (e.g., pulmonary artery, aorta) and veins (e.g., vena cava) range
from approximately 2.7-4.5 dynes/cm
2
. They can reach as high as 32.0 dynes/cm
2
in small arteries and 10.8 dynes/cm
2
in small veins [
95
]. In the microcirculation,
shear stresses are in the range of 1-10 dynes/cm
2
with shear rates from
250-2000 s
-1
[
91
]. It is important to emphasize that these wall shear stresses are
those that would be exerted by the flow of blood over migrating neutrophils or
endothelial cells lining the blood vessel lumens. For non-adherent neutrophils and
other leukocytes within the bloodstream, the magnitudes of shear stresses and
shear rates experienced by these cells are typically lower than those at the wall,
although they can be enhanced by the presence of the surrounding red blood cells.
Within single file capillaries, these shear stresses and shear rates are governed by
the formation of plasma lubrication layer between flowing leukocytes and endo-
thelial cells [
96
].
Conceivably, changes in leukocyte activity under fluid flow stimulation may
occur in response to changes in shear rate or shear stress at the cell surface.
Reportedly, shear rate plays a role in the formation of bonds between leukocytes
and endothelium by enhancing leukocyte displacement toward the vessel wall
[
97
]. On the other hand, the cell deactivating (i.e., mechanobiological) effects of
fluid flow on leukocytes appear to occur in a shear stress, but not shear rate,
dependent fashion [
98
]. Since we are focusing on the mechanoregulation of
neutrophil activity and its putative involvement in obesity-related pathobiology,
we focus on the deactivating effects of shear stress in the subsequent sections.
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