Biomedical Engineering Reference
In-Depth Information
may also be differences between alveolar macrophages, possibly through
different recruitment mechanisms or local factors that may alter their func-
tion, but there are currently no surface markers that allow separation of
subpopulations. Higher density alveolar macrophages are smaller and
appear less mature and may represent the most recently arrived cells. They
have greater chemotactic and phagocytic activity and release greater
amounts of reactive oxygen species and inflammatory mediators than lower
density cells (22). Alveolar macrophages may also be differentiated by
different antibodies which appear to discriminate a more dendritic pheno-
type of cell (23).
B. Dendritic Cells
Dendritic cells are a specialized form of macrophage that play a central role
in the initiation of the innate and adaptive immune response (24). The air-
ways and lungs contain a rich network of dendritic cells that are localized
near the surface, so that they are ideally located to signal the entry of foreign
substances that are inhaled (25). Dendritic cells can activate a variety of
other inflammatory and immune cells, including macrophages, neutrophils,
T- and B-lymphocytes (26). It therefore likely that dendritic cells may play
an important role in the pulmonary response to cigarette smoke and other
inhaled noxious agents and may therefore be a key cellular element in
COPD. The mechanisms by which tobacco smoke actives the immune sys-
tem is not yet understood, but a glycoprotein isolated from tobacco has
powerful immunostimulatory actions (27). There is an increase in the num-
ber of dendritic cells in rat lungs exposed to cigarette smoke (28) and in the
airways and alveolar walls of smokers (29,30). Pulmonary histiocytosis is a
disease caused by dendritic cell granulomata in the lung. It is characterized
by destruction of the lung parenchyma that resembles emphysema and the
adult form of the disease occurs almost exclusively in smokers (31,32). In
mice exposed to chronic cigarette smoke, there is an increase in dendritic
cells in the airways and lung parenchyma (33). The role of dendritic cells
in recruiting other effector cells in COPD deserves further study. MIP-3
a
(CCL20) acts on the chemokine receptor CCR6 that is expressed by imma-
ture dendritic cells and is a potent chemoattractant of dendritic cells. It is
expressed by airway epithelial cells in response to interferon-g (IFN-g)
and therefore may be involved in COPD (34).
IV.
SECRETORY ROLE
Alveolar macrophages have the capacity to secrete a very large number of
inflammatory mediators, including lipid mediators, chemokines, cytokines,
growth factors, and reactive oxygen and nitrogen species. They may there-
fore play many roles in the respiratory tract and may be proinflammatory
