Biomedical Engineering Reference
In-Depth Information
the innate response attract polymorphonuclear neutrophils (PMN), alveolar
macrophages (AM) and natural killer (NK) cells into the damaged tissue
(46-50). Molecules produced by cells at the site of injury (lysozyme, iacto-
ferrin, the surfactant protein A and D, and the defensins) (51-53) as well
as others produced in the liver and transported to the inflammatory site
in the blood (c-reactive protein, mannose binding protein, and compliment
protein C-3) cooperate with these migrating cells to enhance the phagocyto-
sis and the killing properties of the neutrophils and macrophages (46).
Although the innate system has primarily been studied in relation to infec-
tion it is also stimulated to respond by nonliving particulates suspended in
the atmosphere (47,49,50,54). Most of the larger atmospheric particles are
efficiently removed from inhaled air by the filter provided by the upper air-
way but some of these particles trapped in this way are subsequently aspi-
rated into the lower airways during sleep (55). The smaller atmospheric
particles as well the fine particulates generated in tobacco smoke escape
the upper airway filter and are deposited directly in the lungs. The particles
that reach the lower airways from either inhalation or aspiration from the
upper airway provide the major stimulus to for the inflammatory process
responsible for COPD (12).
The alveolar macrophages produce a variety of cytokines as the pha-
gocytose foreign particles deposited on the lung surface that include TNFa,
IL-6, GM-CSF, MIP-1a, and IL-1b (47). The bronchial epithelial cells also
take up these particles and produce LIF, GM-CSF, IL-1a, and IL-8 during
this process (49) and the macrophages and epithelial cells appear to co-
operate to increase local cytokine production (50). Some of these cytokines
(TNFa and IL-1b) function in a paracrine fashion to activate the endothe-
lium and epithelium to express the adhesion proteins that control the migra-
tion of leukocytes (46). Cytokines that enter the blood have an endocrine
function that stimulate the hypothalamus to initiate fever (TNFa and
IL-1b), activate the synthesis of acute phase proteins in the liver (TNFa,
IL-1b, and IL-6) and increase the production and release of leukocytes
and platelets from the bone marrow (TNFa, GM-CSF, and IL-6). The pro-
duction of IL-12 by macrophages also stimulates the NK cells to produce
IFN-g which promotes MHC class 1 and class 11 expressions on surround-
ing cells and induces the macrophages to enhance their respiratory burst.
This IFN-g production promotes the proliferation of antigen stimulated T
cells that initiate the cellular and humoral components of the adaptive
immune response (46).
B. Toll-Like Receptors
New insight into the mechanisms responsible for the initiation of the innate
response has been provided by the discovery of the Toll receptors (56).
These receptors were first discovered in flies (Drosophila) and have
