Adhesion Molecules and Neutrophil Migration - Adhesion Molecules - page 136

Neutrophil A

Integrins
Mac-1
LFA-1
α

PECAM-1

L-selectin

P SGL -1

β

ICAM-1 PECAM-1

P-selectin E-selectin

CD99

JAM-A
JAM-B
JAM-C

Endothelial cell

ESAM

B

Selectins
PSGL1
VLA4

LFA1-ICAM1
VLA4-VCAM1

Activation

MAC1
ICAM1

Transmigration

Tr a nscellular

PECAM1
CD99
JAMS
ESAM

ICAM1
PECAM1

Capture Rolling Slow rolling Arrest Adhesion

strengthening

Intravascular
crawling

Paracellular

Fig. 1 h e neutrophil adhesion cascade. A. Diagram of the major adhesion molecules and
respective ligands involved in neutrophil-endothelial interactions during diapedesis. B. h e key
steps involved in neutrophil migration across the endothelium. h is process begins by capture of
the neutrophils to the wall of the blood vessel, followed by rolling (regulated by selectins), slow
rolling, and then arrest, which is mediated by b2 integrins. Subsequent to arrest, the neutrophils
undergo adhesion strengthening and intravascular crawling. Lastly, neutrophils diapedes across
the endothelium by either a paracellular route (mediated by CD99, JAMs, ESAM, or PECAM-1)
or a transcellular route (ICAM-1, PECAM-1). Adapted from Ley et al. (2007) and Wagner and
Roth (2000). JAMs, junctional adhesion molecules; ESAM, endothelial cell-selective adhesion
molecule; PECAM-1, platelet adhesion molecule 1; ICAM-1, intracellular adhesion molecule 1.

mRNA and protein synthesis. It is inferred that E-selectin is responsible for
maintaining neutrophil rolling at er downregulation of P-selectin. Interestingly,
L-selectin and P-selectin require shear stress to support adhesion (Yago et al.
2007), which may explain why selectins are not involved in neutrophil-epithelial
interactions.
Subsequent to rolling is 'slow rolling, a process mediated by selectin-triggered
signaling (Ley et al. 2007, Zarbock and Ley 2008, Zemans et al. 2009). Slower
rolling velocities prolong the time of neutrophil interaction with endothelial cells,
which in turn conducts the proper activation of neutrophils and successful arrest.
h e arrest of neutrophils at the endothelial surface is an essential step and involves
the interaction of β 1 and β 2 integrins and their cognate binding partners. h us,
when rolling neutrophils receive the appropriate trigger through selectin and/or
chemokine receptor engagements, integrin activation is initiated. Integrins are