Biomedical Engineering Reference
In-Depth Information
D. Macrophage Clearance
Alveolar macrophages are presumed to be cleared from the airways predo-
minantly by mucociliary clearance, which is significantly impaired in
patients with COPD. Macrophages may also be cleared via lymphatic drai-
nage, and this might also be impaired in COPD patients as a result of
emphysema and fibrosis of small airways interrupting lymphatic channels.
III. MACROPHAGE HETEROGENEITY
There is increasing evidence for distinct populations of macrophages that
may play different roles, although the tools that can differentiate these
subpopulations are poorly developed.
A. Alveolar and Interstitial Macrophages
At least two subpopulations of macrophages are found in the lungs (20,21).
Alveolar macrophages are localized to the alveolar spaces and are strategi-
cally placed to interact with inhaled pathogens and particles. Interstitial
macrophages make up about half of the total numbers of macrophages in
the lung and are located within the alveolar walls and in airway walls. This
location may give them an important role in the regulation of matrix pro-
teins in the lung. Interstitial macrophages may represent an intermediary
stage in the maturation of alveolar macrophages from monocytes recruited
from the pulmonary circulation. Alveolar macrophages are large mature
cells with a high cytoplasm
=
nucleus ratio and resembling other tissue
macrophages, whereas interstitial macrophages are smaller, more uniform
in size, contain few intracytoplasmic lamellar inclusions or lysosomes, and
more closely resemble peripheral blood monocytes. There is increasing evi-
dence that alveolar and interstitial macrophages are distinct cell populations
with differing functions and that each population may contribute to inflam-
matory and immune responses in the lungs. Alveolar macrophages release
more inflammatory mediators and show increased chemotaxis, phagocyto-
sis, cytotoxicity, and release of reactive oxygen and nitrogen intermediates
than interstitial macrophages. Interstitial macrophages express greater
quantities of complement C3 receptor and intercellular adhesion molecule-1
(ICAM-1), are more active in secreting interleukin (IL)-1 and IL-6 and
exhibit greater Ia antigen expression, suggesting that they are more specia-
lized in immune responses and immunoregulation. They may also have a
greater capacity to proliferate compared to alveolar macrophages and this
may maintain the lung macrophage pool. There is a need to further investi-
gate the differences between alveolar and interstitial macrophages, particu-
larly in COPD patients; alveolar macrophages may be obtained by
bronchoalveolar lavage, whereas interstitial macrophages may be isolated
by digestion of lung parenchyma removed at surgical resection. There
