Biology Reference
In-Depth Information
trienes, prostaglandins, vitamin D metabolites, IL-1, and TGF-b (Strickland et
al., 1994; Upham et al., 1995).
Other Alveolar Macrophage Surface Receptors
AM communicate with external environment via surface receptors, which are
capable of binding speci®c ligands and activate various signal transduction
pathways to produce di¨erent biological functions. Many surface receptors
have been de®ned in AM. ( Bezdicek and Crystal, 1997). AM express CD14,
the receptor for bacterial LPS, although generally lower levels compared with
peripheral blood monocytes. Additional examples include receptors for trans-
ferrin, histamine, b-adrenergic agonists, neutrophil elastase, cathepsin G,
a1-antitrypsin, PMA, and surfactant proteins (Lohmann-Matthes et al., 1994;
Sibille and Reynolds, 1990; Shepherd, 1991). This diversity of surface receptors
allows AM to respond to a vast array of environmental and local in¯uences.
Signal Transduction Pathways
As most available studies on intracellular signaling pathways utilize monocytes
or monocyte-derived macrophages, the signal transduction pathways of AM
are incompletely understood. AM express many of the surface receptors ex-
amined in other mononuclear phagocytes and neutrophils. The consequences
of membrane receptor triggering of AM likely involves one or more second
messenger pathways.
Investigtors have recently examined speci®c signal transduction pathways
in human AM. Recognizing the importance of the nuclear factor (NF )-kB/I-kB
pathway in cytokine regulation, LPS stimulation of AM results in NF-kB
activation (Mathys et al., 2000). Furthermore, LPS-mediated NF-kB induction
and the release of IL-6, IL-8, and TNF from human AM is dependent on
tyrosine kinase and phosphatidylcholine-speci®c phospholipase C, and inde-
pendent of protein kinase C (Carter et al., 1998). Furthermore, two members of
the mitogen-activated protein kinases (MAPKs), extracellular signal-regulated
kinase (Erk) and p38 kinase, are also necessary for LPS-mediated IL-6 and
TNF transcription and cytokine release (Carter et al., 1999).
MOLECULAR AND BIOLOGICAL CHARACTERISTICS OF HIV-1
A detailed discussion of HIV-1 is included in other chapters of this topic, and
comprehensive reviews of HIV-1 biology are available to the reader (Fauci,
1996; Greene, 1991; Rich, 1998). This section will provide an overview of
important molecular and biological characteristics of HIV-1 as these relate to
AM.
HIV, a lentivirus in the Retroviridae family that infects humans, is the major
cause of the acquired immunode®ciency syndrome (AIDS). The related HIV-2
