Biology Reference
In-Depth Information
interferon-g (IFN-g), granulocyte-macrophage colony-stimulating factor
(GM-CSF ), interleukin (IL)-2, lipopolysaccharides (LPS), phorbol myristate
acetate ( PMA), leukotriene B4 ( LTB4), formyl-methionyl-leucyl-phenylalanine
(f-MLP), and platelet activating factor ( PAF) ( Reed et al., 1987; Sibille and
Reynolds, 1990), although whether such activating signals are operant in vivo
in the lungs remains to be established. The consequences of activation are not
the same for every activation signal, and the hierarchy of activation responses
of AM has not been de®ned.
Macrophage Secretory Products
AM release a variety of products, including oxidants, antioxidants, growth
factors, enzymes, proteases, antiproteases, and bioactive lipids, that allow AM
to regulate and maintain the integrity of the lungs ( Kelley, 1990; Nathan, 1987;
Sibille and Reynolds, 1990; Takemura and Werb, 1984). For a comprehensive
review of the spectrum of macrophage secretory products, the reader is referred
to several excellent reviews ( Kelley, 1990; Sibille and Reynolds, 1990). Among
the more important secretory products involved in antimicrobial function are
the reactive oxygen species including superoxide anion, hydrogen peroxide,
and hydroxyl radical, which are oxygen metabolites of the membrane-bound
NADPH-oxidase system. AM also release nitric oxide, which may participate
in antimicrobial function and mediate in¯ammation ( Kuo et al., 2000).
Cytokines and Cytokine Receptors
AM can also produce a variety of cytokines including IL-1, IL-6, IL-8, IL-10,
IL-12, TNF-a, IFN-g, macrophage colony-stimulating factor (M-CSF ), GM-
CSF, and transforming growth factor ( TGF )-b (Kelley, 1990; Nathan, 1987).
AM also express several cytokine receptors including receptors for IFN-g,
TNF-a, IL-2, IL-4, and GM-CSF. AM function can be regulated by individ-
ual cytokines or combinations of cytokines interacting with speci®c surface
receptors. As AM secrete speci®c cytokines and also express the appropriate
receptor, some cytokines serve an autocrine function. A broad range of bio-
logical e¨ects can be induced by the binding of di¨erent cytokines to their spe-
ci®c receptors.
Accessory Cell Function
In general, AM are less potent antigen-presenting cells compared with other
macrophages such as Langerhans cells and peritoneal macrophages ( Roth and
Golub, 1993). AM are de®cient at presenting tetanus toxoid to autologous
CD4
T lymphocytes, a de®ciency that may be attributed to failure to express
the costimulatory molecules B7-1 and B7-2 (Chelen et al., 1995). AM may
suppress immune responses by producing a variety of mediators that may in-
hibit T-lymphocyte proliferation such as superoxide anion, nitric oxide, leuko-
