Biomedical Engineering Reference
In-Depth Information
separately, it is clear that there is a complex interaction between these
inflammatory cells and mediators (Fig. 2). Indeed, it is likely that there is
a cascade of inflammation, initiated by cigarette smoking indicating that
innate immune cells of the airway, namely macrophages and epithelial cells,
then release chemokines to recruit cells from the circulation into the lung,
including monocytes (which differentiate into macrophages), neutrophils
and T- and B-lymphocytes (Fig. 3). There is now much research identifying
the specific chemotactic factors involved as this may represent a novel ther-
apeutic approach. In addition to chemotactic mediators, other mediators
induce inflammatory responses, whereas others induce structural changes
Figure 2
Inflammation in COPD is complex with may activated inflammatory and
structural cells that release multiple mediators, including lipid mediators such as
leukotriene B
4
(LTB
4
) which is chemoattractant for neutrophils. Chemokines such
as monocyte chemotactic protein (MCP)-l and macrophage inhibitory protein
(MIP)-l
a
which attract monocytes, interleukin (IL)-8, and growth-related oncogene
(GRO)-
a
which attract neutrophils and monocytes, interferon inducible protein
(IP)-10 which attracts CD8
รพ
cells, reactive oxygen species (ROS), and nitric oxide
(NO). Granulocyte-macrophage colony stimulating factor (GM-CSF) which pro-
longs neutrophils survival. Tumor necrosis factor (TNF)-
a
which amplifies inflam-
mation by switching on multiple inflammatory genes and may also account for
some of the systemic effects of the disease. Endothelin and transforming growth fac-
tor-
b
(TGF-
b
) which induce fibrosis. In addition multiple proteinases are releases
that result in elastolysis, including the serine proteinases neutrophils elastase and
proteinase C, cathepsins and matrix metalloproteinases (MMP). This combination
of mediators that attract and activate inflammatory cells and proteinases which cause
elastolysis and mucus hypersecretion result in the typical pathophysiology of COPD.
