Biomedical Engineering Reference
In-Depth Information
gamma-catenins as well as signaling molecules that facilitate the connection
to the cytoskeleton (46,47). When the adherens junction is disrupted, the
tight junction is also affected. It is thought that junctional deterioration
leads to a progressive decrease in epithelial integrity and induces alterations
in epithelial morphology, with consequent enhanced paracellular transit of
antigens and pathogens (48). The main cell-cell adhesion molecule is
E-cadherin. The cadherins are thought to be critical to the development
of all solid tissues. The roles of cadherins during development have been
recently reviewed (49-51). The best-described cadherins are E-cadherin
(epithelial), N-cadherin (neural), P-cadherin (placental), and L-CAM (liver
cell adhesion molecule). E-cadherin is expressed very early in embryonic
development and is primarily expressed on epithelial cells in adult tissues.
In the human bronchus and alveolus, E-cadherin is expressed at intercellular
contacts of epithelial cells and particularly at the lateral aspects of columnar
cells (52). This location of E-cadherin is consistent with the location of inter-
mediate
=
adherens junctions that interact with actin filaments of the cytoske-
leton. P-cadherin has been identified in bronchial epithelium but not in
alveolar epithelium (53,54).
The expression and function of cadherins are modulated in inflamma-
tion and disease states. Kasper and Muller have described cadherin expres-
sion in several animal models of lung injury. Using a pan-cadherin antibody,
they found that radiation injury of the lung caused increased cadherin
expression in bronchial epithelial cells, interstitial cells, and type II pneumo-
cytes (55). Using an antibody to E-cadherin, they found human lung speci-
mens with fibrosis demonstrated spotty, cytoplasmic staining of alveolar
epithelial cells rather than the normal basolateral membrane staining (56).
McGuire et al. have shown that E-cadherin is a substrate for matrilysin
and suggest that shedding of E-cadherin ectodomain is required for epithe-
lial repair (57). The results imply that modulation of cadherin expression
and function is important during repair and remodeling of the epithelium.
Proinflammatory cytokines alter the function of cadherins and thus cause
disrupted epithelial integrity (58,59). Histamine is capable of altering cad-
herin function and may thus be involved in increased epithelial permeability
in allergic inflammation (60).
Desmosomal cadherins are another group of transmembrane adhesion
molecules that are involved in cell-cell adhesion and are found in desmo-
somes. Green and Jones have reviewed the structure and function of desmo-
somes (61). Similar to the other cadherins described above, desmosomal
cadherins, including desmocollins and desmogleins, are calcium-dependent
transmembrane adhesion molecules that participate in homotypic cell-cell
adhesion. The exact role of desmosomal cadherins in adhesion is not yet
clear, however. Desmosomal cadherins apparently have a functional
complexity that the classical cadherins, such as E-cadherin, do not have.
Three desmocollin and three desmoglein genes have been identified
