Biology Reference
In-Depth Information
CELLULAR AND MOLECULAR FEATURES OF
ALVEOLAR MACROPHAGES
Several excellent comprehensive reviews of AM are available to the reader
( Bezdicek and Crystal, 1997; Brain, 1990; Fels and Cohn, 1986; Lohmann-
Matthes et al., 1994; Sibille and Reynolds, 1990). This section will provide a
brief overview of several important characteristics and features of AM.
AM are the most abundant nonparenchymal cells in the lungs, with an esti-
mated 50±100 AM per alveolus (Crapo et al., 1982) and account for >85% of
nonadherent immune cells in the alveolar airspace (Fels and Cohn, 1986). AM
are predominantly derived from circulating peripheral blood monocytes and
di¨erentiation as the monocytes traverse the alveolar interstitium under the in-
¯uence of cytokines and growth factors ( Thomas et al., 1976). Recruitment of
monocytes into alveoli is regulated by monocyte-speci®c chemoattractants such
as macrophage in¯ammatory protein-1 (MIP-1) and MIP-2 ( Brieland et al.,
1993; Iyonaga et al., 1994), and integrin-mediated interactions. Often referred
to as a uniformly functioning population of cells, AM obtained by broncho-
alveolar lavage likely represent a heterogeneous group of cells ( Brain, 1988).
Local proliferation accounts for only
a
2% of the expansion of alveolar mac-
rophages ( Bitterman et al., 1984), although AM are generally long-lived with
estimated life spans of months to years (Marques et al., 1997).
AM perform a number of antimicrobial and anti-in¯ammatory functions.
AM are an important component of the innate immune response, and may in-
¯uence the nature of the acquired immune response to antigen ( Fearon and
Locksley, 1996). AM eliminate inhaled microorganisms, clear environmental
toxins, and remove cellular debris. AM also express a broad range of secretory
products and mediate a variety of essential biologic activities in the context of
antimicrobial activity, acute in¯ammatory response and tissue repair.
Antimicrobial Function
AM are ``professional'' tissue phagocytes and thus require the essential com-
ponents of chemotaxis, binding, ingestion, and digestion. AM are capable of
chemotaxis, the directed movement along a concentration gradient (Sibille and
Reynolds, 1990). Chemoattractants such as N-formylated peptides, leucotriene
B4, and C5a induce macrophage migration upon binding to speci®c receptors
expressed along the leading edge of the cell surface. AM binding of particles
can be nonspeci®c or enhanced through interaction of speci®c AM receptors
with native molecules or opsonins decorating the particles.
Macrophages ingest or internalize molecules and small particles (< 1 mm,
endocytosis), and ¯uid ( pinocytosis) via a clathrin-associated actin-independent
process, and larger particles (> 1 mm) via actin-dependent processes (Anderson
et al., 1990; Greenberg and Silverstein, 1993; Orosi and Nugent, 1993; Wright
and Detmers, 1991). Ingestion requires the formation of lamellipodia and pseudo-
podia, generated by assembly and cross-linking of actin ®laments. Human AM
