Biology Reference
In-Depth Information
are unique phagocytes in their dependence on an oxygen tension > 25 mm Hg
for optimal phagocytosis ( Hunninghake et al., 1980).
Ingestion is greatly facilitated by a variety of receptors expressed on the
surface of AM. Opsonin-independent internalization is mediated through pat-
tern recognition receptors such as mannose receptor ( Ezekowitz et al., 1990)
and scavenger receptor ( Palecanda et al., 1999). These receptors recognize cer-
tain patterns of molecules expressed on the surfaces of particles or pathogens,
and thus represent an important component of innate immunity. The family of
complement receptors (CR1, CR3, and CR4) represent another component of
the innate immune response facilitating phagocytosis by an opsonin-dependent
process (Sibille and Reynolds, 1990; Unkeless and Wright, 1988). AM expresses
CR1 receptor, which preferentially binds complement component C3b but also
could bind C3bi and C4b. Opsonin-dependent internalization is also mediated
through the family of Fcg receptors, including FcgIa receptor (high a½nity),
FcgII (low a½nity), and FcgIIIa. These well-characterized phagocytic receptors
recognize the Fc domain of immunoglobulin G (IgG), and mediate phago-
cytosis, superoxide production, and release of cytokines such as tumor necrosis
factor ( TNF )-a. AM do not have receptors for IgM although IgM immune
complexes can bind via C3b (Gadek et al., 1980).
Finally, digestion or killing can occur by oxidative and nonoxidative mech-
anisms. Intracellular release of reactive oxygen intermediate species (i.e., oxi-
dative bust response, or respiratory burst response) is a major microbicidal
mechanism employed by AM. Production of reactive oxygen intermediates is
myeloperoxidase (MPO) independent. By this mechanism, the principle toxic
reactants formed are hydroxyl radical and singlet oxygen, which are derived
from the interaction of O
2
ÿ
and hydrogen peroxide ( H
2
O
2
). AM could also
use nonoxidative microbicidal mechanisms by expressing macrophage cationic
proteins, lysozyme, and other lysosomal enzymes such as elastase, plasminogen
activator, and phospholipase to digest microorganisms (Orosi and Nugent,
1993). Disorders of any of these four critical components can result in serious
host defense diseases such as pneumonia ( Brown and Gallin, 1988).
Alveolar Macrophage Activation
AM can become activated by a variety of stimuli, both speci®c stimuli through
speci®c receptors and nonspeci®c stimuli. Some activation signals initiate a
broad spectrum of processes, whereas other signals result in limited responses.
The mechanisms of AM activation are incompletely understood, although
activation results in changes in morphology and general metabolic activity,
changes in the density of surface molecules, and the release of a variety of
molecules, including cytokines, bioactive lipids, oxidants, lysosomal enzymes,
and growth factors. Activated macrophages are bigger, with more pronounced
ru¿ing of the plasma membrane, increased numbers of pseudopodia, and in-
creased pinocytotic vesicles. The resting metabolic activity of AM is high and
increases further with activation. Activation signals include immune complexes,
