Biomedical Engineering Reference
In-Depth Information
involved in leukocyte adhesion to endothelium: the β
2
leukocyte integrins (CD11a/
CD18, CD11b/CD18 and CD11c/CD18, the β
1
integrin VLA-4 (CD49d/CD29)
and α
4
β
7
.
h e expression of the β
2
integrin is coni ned to leukocytes, but among subtypes of
leukocytes the distribution on CD11/CD18 dif ers. For example, peripheral blood
lymphocytes express primarily CD11a/CD18, whereas neutrophil, monocytes and
natural killer cells express all three β
2
integrins. Surface expression of CD11b/
CD18 and CD11c/CD18 is increased by a variety of stimulus, FMLP, GM-CSF, C5a,
TNF-α, and LTB4. Ligands for the leukocyte integrin include proteins expressed
by cells (ICAM-1CD11a/CD18, CD11b/CD18; ICAM-2 CD11a/CD18; ICAM-3
for CD11a/CD18) as well as soluble proteins (i brinogen and factor X for CD11b/
CD18 and complement fragment for CD11b/Cd18 and CD11c/CD18). Neutrophil
and monocyte adhesion to endothelium relies primarily on the CD11a/CD18 and
CD11b/CD18 leukocyte integrins with only a minor role for CD11c/CD18 (Hynes
et al.
1992, William 1988, Arnaout 1990).
Other Adhesion Pathways
CD11b/CD18 was initially identii ed as a receptor for iC3b. CD11b/CD18-
dependent neutrophil adhesion to endothelium was shown to be rapidly induced
by i xation of complement on the endothelial surface (Mark
et al.
1989, Collard
1999).
Fibrinogen is a soluble ligand for CD11b/CD18. Recently, i brinogen was
shown to promote leukocyte adherence to endothelium by binding both leukocyte
and endothelial cells.
REGULATION OF ENDOTHELIAL ADHESION MOLECULE
EXPRESSION
Among the endothelial adhesion molecules there are both similarities and dif erences
regarding the stimuli that induce them and the temporal relation of their expression.
For example, a triad of agents, IL-1, TNF-α, and lipopolysaccharide, stimulate the
expression of ICAM-1, VCAM-1 and E-selectin, but the kinetics of the induced
surface expression in vitro dif ers, with E-selectin having a shorter half-life than
ICAM-1 or VCAM-1. Stimulated surface expression of ICAM-1, E-selectin, and
VCAM-1 appears to result in large part from increased transcriptional regulation.
However, surface expression of P-selectin may also involve a rapid mobilization
of cytoplasmic granules induce by non-cytokine agents, and surface expression
of E-selectin is in part regulated by rapid internalization. h erefore, important
dif erences in regulatory mechanisms exist among these proteins that may help to
explain the recruitment of subsets of leukocytes to specii c sites of endothelium
during an inl ammatory or immune response (Ellist 1990, Smith 1993, McEver
et al.
1989).
