Biomedical Engineering Reference
In-Depth Information
proposed that these structural cells play not only an amplifying role, but
also rather a central role in creating a web of cytokines that control chronic
inflammation in the tissue microenvironment.
B. Cell-Cell Interactions
Epithelial cells also participate in inflammatory processes by directly inter-
acting with leukocytes. Epithelial cells can express MHC antigens (161-
163). Increased expression of MHC antigens on bronchial epithelial cells
has been described in chronic bronchitis and correlates with the amount
of inflammation (164). Expression of MHC antigens allows cells to directly
interact with lymphocytes and raises the possibility that epithelial cells can
present antigen to lymphocytes. Both MHC class I (HLA-A,B,C in humans)
and MHC class II (HLA-DR, DQ, DP in humans) antigen expression are
regulated on a variety of epithelial cell types. The most potent stimulant
for expression is likely
g
-IFN.
Epithelial cells express cell surface molecules that enhance cell-cell
adhesion with leukocytes. A number of investigations have emphasized
the importance of the expression of intercellular adhesion molecule-1
(ICAM-1) by epithelial cells (170). The ICAM-1 is the ligand for LFA-1
on leukocytes (165). The interaction of ICAM-1 with LFA-1 is thought
to strengthen the cell-cell adhesion mechanisms during activities such as
antigen presentation, target recognition, and leukocyte transmigration
(166-168). The expression of ICAM-1 is enhanced on airway epithelial cells
by proinflammatory cytokines (169-171). The IL-1ß, TNF-
a
,
g
-IFN, and
IL-4 are cytokines that are implicated in the expression enhancing activity.
The expression of ICAM-1 may be coordinated with local binding of
IL-8, creating an area that facilitates leukocyte migration (172,173). The
expression and function of adhesion molecules such as ICAM-1 is also
modulated by viral infection (174,175). The ability of the cells to express
ICAM-1 in the setting of a viral infection may be an important component
of the defense mechanism to clear such infections. The ICAM-1 expression
is increased in chronic bronchitis (164,176). So, in addition to producing
neutrophil chemotactic factors, epithelial cells express an adhesion molecule
that promotes neutrophil transmigration into the airway.
V. WOUND REPAIR AND REMODELING
A.
Epithelial Repair
Inhalation of toxins and irritants, e.g., cigarette smoke, with damage to the
epithelium is a major pathogenic process in COPD. Repair processes are
initiated as part of the inflammatory response. If normal epithelial and
tissue structure is restored or preserved, then normal tissue function should
also be preserved. If normal tissue structure is not restored, then dysfunction
