Biomedical Engineering Reference
In-Depth Information
and collagen by bronchial epithelial cells is increased by TGF-
b
(196). The
TGF-
b
is an important mediator of wound repair and has been the subject
of recent reviews (221,222). Although not studied extensively, TGF-
b
expression is thought to be increased in bronchitis (223).
Epithelial cells have important interactions with mesenchymal cells.
When bronchial epithelial cells were examined for ability to produce factors
that subsequently modulated matrix production by fibroblasts in vitro, both
stimulatory and inhibitory factors were found (199,224-226). The stimula-
tory factor is composed, in part, of TGF-
b
. The inhibitory activity produced
by bronchial epithelial cells appeared to be PGE2, capable of inhibiting
collagen production by fibroblasts. Thus, mediator ''networking'' is likely
operating in the control of matrix production in epithelia. Epithelial cells
also modulate fibroblast recruitment, proliferation, and contraction of
matrix (227-229). Bronchial epithelial cell-conditioned medium stimulates
fibroblast proliferation. The growth stimulatory activity in the conditioned
medium is heterogeneous, including peptides, eicosanoids, and TGF-
b
(224). Some of the mediators that drive epithelial repair also drive fibroblast
accumulation. Fibronectin is a wound component that attracts and supports
epithelial cell survival (230). Fibronectin is also an attractant for fibroblasts
(199). Epithelial cells may also influence peribronchial tissue through fibro-
blast-mediated contraction of collagenous matrix. Bronchial epithelial cells
release mediators that enhance collagen gel contraction by fibroblasts in
vitro (228). The importance of epithelial and mesenchymal interactions
has lead to the development of in vitro models of the airway that include
both cell types (224,231).
Both epithelial cells and fibroblasts express proteolytic enzymes that
modulate extracellular matrix (232-234). Studies in several cell systems
suggest that the underlying matrix proteins play crucial roles in directing
this process of migration and differentiation (233,235). Recent studies are
beginning to address the roles of matrix metalloproteinases in COPD
(236-241). It appears that expression of certain metalloproteinases such as
MMP-9 is increased in epithelium and may play a role in remodeling.
Agents which modulate the function of metalloproteinases would be just
one of many possible therapeutic approaches for peribronchial fibrosis.
So far, we have discussed repair in the context of airway remodeling
but similar concepts likely apply to defective repair of alveolar walls in
emphysema. The alveolar epithelial response to injury likely resembles that
of the airway epithelium in many respects. Disrupted alveolar epithelial
repair may contribute to the loss of alveolar walls in emphysema. Some
of the same factors that promote bronchial epithelial repair also promote
alveolar epithelial cell recruitment and proliferation following injury
(242,243). Alveolar epithelial cells also communicate with mesenchymal
cells. Fibroblasts can function as a bridge from endothelial cells to epithelial
cells (244).
