Biomedical Engineering Reference
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Fig. 1 Neutrophil
pseudopods. Representative
micrographs of quiescent
(untreated) cells and cells
activated with 10 nM fMLP
to extend pseudopod(s).
Green staining indicates
nuclei labeled with selective
deoxyribonucleic acid
marker, 4',6-diamidino-2-
phenylindole (DAPI). Arrows
indicate the presence of
extended pseudopods.
Magnification: 400x
the endothelium [
10
,
67
,
72
,
73
]. In doing so, neutrophils extravasate and migrate,
via a multi-step chemotactic-driven process, to the site of tissue damage or
infection (Fig.
2
).
Notably, during acute inflammation, neutrophils become activated by chemo-
kines released from inflamed endothelium [
74
] that stimulate surface expression
and activity of b2 (i.e., CD18) integrins [
74
-
76
]. The two principal CD18 integrin
heterodimers expressed on the neutrophil surface are lymphocyte function-asso-
ciated antigen-1 (CD11a/CD18) and macrophage-1 antigen (CD11b/CD18).
Whereas CD11a/CD18 integrins are more involved in early, loose-capture inter-
actions that arrest the rolling neutrophil, CD11b/CD18 plays a critical role in
ensuring firm attachment of neutrophils to the venular wall [
77
,
78
]. These key
adhesive interactions allow the neutrophil to remain in close proximity to, or in
contact with, the vascular endothelium under the venular blood flow environment
(Fig.
2
). Moreover, these cell-cell adhesion molecules allow the adhered neutro-
phils to withstand the shearing forces of the surrounding blood flow that act to
dislocate them from the vessel wall [
67
]. In line with this role, CD18 integrins are
essential for neutrophil recruitment during inflammation, as demonstrated by
knockout murine models [
79
-
82
].
Together, these changes in surface biochemistry, deformability, and geometry
of the neutrophils greatly facilitate their mobilization out of the bloodstream [
10
].
But, at the same time, these changes in the neutrophil activation state within
the bloodstream have more than just a biochemical impact on the circulation.
Neutrophil activation also has a biophysical impact, particularly on local hemo-
dynamics of the microvasculature. In this way, the state of the regulatory mech-
anisms that control neutrophil activity has a potential influence on tissue perfusion
and tissue health.
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