Biomedical Engineering Reference
In-Depth Information
strain do not protect against another (62) and a specific decrease in the
peripheral blood T lymphocyte proliferation to challenge with a well
conserved OMP of H. influenzae (OMP P6), appeared to increase the suscept-
ibility to H-Flu induced exacerbations (61). Transgenic mouse experiments
indicate H. influenzae can induce an innate response by interacting with
TLR-4 (63) and it is conceivable that this type of response might induce some
of the exacerbations of COPD.
D. Remodeling
The remodeling process that repairs the damage associated with the chronic
innate and adaptive immune response in the airways tissue is most closely
associated with the decline in lung function in COPD (36). Very little is
known about the fundamental mechanisms involved in airway remodeling
but it is reasonable to assume that it is similar to the repair process during
the healing of wounds. Studies of wound healing indicate that activation of
the myofibroblasts to secrete new extracellular matrix (ECM) is a key fea-
ture of the tissue repair in wound healing (64). The myofibroblasts are a
group of cells of uncertain origin that share features of both fibroblast
and smooth muscle cells. They were first described in the lung by Kapanci
et al. (65) and are now known to be widely distributed in body tissues where
they play a central role in the initiation and control of the inflammatory
repair and remodeling processes. Myofibroblasts are capable of synthesizing
prostaglandins and expressing both the constitutive cyclooxygenase-1
(COX-1 or PHS-1) gene product and the inducible COX-2 (PHS-2) protein
(66-70). They are also avid producers of chemokines and cytokines and
express
a
and
b
integrins that provide adherence to matrix proteins
(71-74). When activated, they express intracellular adhesion molecule-1
(ICAM-1), vascular cell adhesion molecule (VCAM-1), and other adhesion
molecules that allow lymphocytes, mast cells, and neutrophils to dock on
their surface (64). Walker and his associates have shown that a stellate
myofibroblast phenotype populates the interstitial space of the alveolar wall
and sends extensions though the endothelial and epithelial basement
membranes to make contact with these cells (75-78). This arrangement sug-
gests that the stellate myofibroblast phenotype may be the ''quarterback''
that directs inflammatory cell traffic through the interstitial compartment
of normal peripheral lung tissue.
Figure 6 has been modified from the review of Powell et al. (64) to
indicate that an activated myofibroblast phenotype capable of synthesizing
matrix may arise from stem cells, fibroblasts, and the stellate form of the
myofibroblast. The activated phenotype differs from the other forms in that
it expresses a-SM actin, has a reduced number of vitamin A lipid droplets
and a more expanded rough endoplasmic reticulum than the other forms.
It also has fewer extensions and less contact with other cells than the stellate
