Biomedical Engineering Reference
In-Depth Information
A.
Inflammatory Mediators
The ability of airway epithelial cells to produce inflammatory mediators has
been of interest in asthma and is receiving more interest in the study of
chronic bronchitis and COPD (113,117,118). Airway epithelial cells produce
a variety of proinflammatory mediators, including chemotactic cytokines,
eicosanoids, growth factors, and nitric oxide (118).
The idea that epithelial cells function as a first line of defense is
supported by the observations that epithelial cells are capable of releasing
mediators relatively quickly after stimulation or damage. Koyama et al.
(119) have shown that cultured bovine bronchial epithelial cells release
arachidonate metabolites including LTB4 within 1 hr of exposure to endo-
toxin. Other chemotactic activities for neutrophils and monocytes were
released at later time points (119). The release of arachidonate metabolites
may be a rather general, early response of airway epithelial cells to injury
as many stimuli will elicit LTB4 release from bovine bronchial epithelial
cells in primary culture. Viral
infection and ozone are just two of the
described stimuli (120,121).
Epithelial cells also participate in more chronic inflammatory
processes. Some hours after stimulation, airway epithelial cells release very
potent chemotactic factors for neutrophils that likely play roles in the
chronic attraction of leukocytes. The cytokine with perhaps the most potent
chemotactic activity for neutrophils is IL-8 (122). The IL-8 is thought to
have a relatively long half-life (123). The IL-8 is one member of a family
of similarly sized (8-10 kDa) chemokines called the CXC chemokines. The
release of CXC chemokines by airway epithelial cells is modulated by other
cytokines. It has been shown that interleukin-17 (1-1000 ng
=
mL) increases
the release of the CXC chemokines GCP-2, GRO-
a
, and IL-8 in a concen-
tration-dependent manner (124,125). Epithelial cells also release chemokines
of the C-C family, including RANTES, MCP-1, and eotaxin (126). These
chemokines have more activity on macrophages (127-132) and their release
is also modulated in inflammation (133). Epithelial cells release other cyto-
kines such as IL-1, IL-6, and IL-18. Airway cells release GM-CSF in vitro
(134-137), which is capable of promoting survival and activation of eosino-
phils, stimulating neutrophils, and stimulating-macrophage proliferation.
Ohtoshi et al. (135) have demonstrated that epithelial cells from inflamed
tissues release more GM-CSF than do cells from normal tissues. It is
thought that epithelial cells interact with other cells to augment production
of mediators such as GM-CSF (138). Thus, epithelial cells from inflamed
tissues release factors that recruit, activate, and differentiate leukocytes.
Important to the theme of COPD is the observation that epithelial
cells release inflammatory mediators in response to air pollutants. Nitrogen
dioxide, ozone, and diesel exhaust particles have been studied (117,139). The
magnitude of response of epithelial cells may be modified in COPD such
