Biomedical Engineering Reference
In-Depth Information
adhesive interaction at the epithelial basolateral surface (Ostermann
et al.
2002,
Chavakis
et al.
2004).
As CD11b/CD18 can also bind to carbohydrates it is not surprising that several
carbohydrate interactions are recognized to be involved in neutrophil transepithelial
migration. However, the role of carbohydrates in neutrophil transmigration occurs
at er i rm adhesion has been established. Fucoidin, for example, was found to
potently inhibit epithelial cell binding to CD11b/CD18, implying that fucosylated
proteoglycans are expressed on the epithelial cell surface (Colgan
et al.
1995). At
present, however, the specii c molecules that bind to CD11b/CD18 have yet to be
identii ed.
As neutrophils migrate across epithelial monolayers, they exclusively travel
paracellularly. An important mediator of this transmigration step is CD47,
which is expressed on the basolateral surface of epithelial monolayers as well as
on neutrophils (Parkos
et al.
1996). While both the epithelial cell and neutrophil
CD47 are involved in directing neutrophil migration across the epithelium, the
role of epithelial CD47 in facilitating this migration event has yet to be determined.
However, during transepithelial migration, neutrophil CD47 has been found to
be redistributed to the neutrophil cell membrane where subsequent ligation of
CD47 triggers downstream signaling pathways that enhance neutrophil migration
by modifying the epithelial cell cytoskeleton. In addition, CD47 binds SIRPα
in
cis
and such interactions, to a certain extent, regulate neutrophil transepithelial
migration. For example, SIRPα interacts with SHP-1 and SHP-2 and it is inferred
that these interactions induce signal transduction cascades that enhance the rate
of neutrophil transepithelial migration. Moreover, SIRPα family members may
also mediate neutrophil transepithelial migration in a CD47-independent fashion
as SIRPα1, which is not a CD47 ligand, regulates neutrophil transmigration (Liu
et al.
2002b). It has also been proposed that neutrophil SIRPα binds epithelial
CD47
in
trans
, which may also initiate the responses in the epithelium to facilitate
paracellular movement of the neutrophils. Adding yet another layer of complexity,
neutrophil transepithelial migration is additionally mediated by JAM-like protein
(JAML) (Moog-Lutz
et al.
2003). Recent studies have found that JAML binds to the
coxsackie and adenovirus receptor (CAR), an Ig superfamily receptor expressed at
epithelial tight junctions (Zen
et al.
2005).
Once the neutrophils have completely traversed the epithelial monolayer they
are retained on the apical surface of the epithelium and then cleared. Retention
of neutrophils at the epithelial cell surface serves as a defense barrier, which
allows for the destruction of invading microorganisms. h us, neutrophils must
participate in adhesive interactions at the apical epithelial surface. As ICAM-1
is expressed at the apical surface of epithelial cells and this adhesion molecule
is a known ligand for CD11b/CD18, it is tempting to speculate that ICAM-1
tethers neutrophils at mucosal surfaces. Lastly, neutrophils must be cleared
from the apical surface of epithelial cells since prolonged exposure to activated
