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(Downing et al., 1995) and HIV-infected persons with active pulmonary disease
(Phelps and Rose, 1991), the speci®c role of AM in this process has not been
established. Furthermore, whether elevated SP-A levels facilitate or impair AM
function remains to be established, and whether facilitated SP-A-mediated
binding of pathogens ( Downing et al., 1995; Williams et al., 1997) contributes
to pathogenesis of infection remains to be determined. Some investigations
suggest that pathogens may utilize host-derived SP-A to avoid recognition by
host immune cells ( Koziel et al., 1998b).
Surface Expression of Receptors
Increasing evidence suggests that surface receptor expression may be altered on
AM from HIV-infected persons. Surface-associated macrophage mannose re-
ceptor is reduced in asymptomatic HIV-infected individuals (Koziel et al.,
1998a), whereas the soluble form of the receptor is greatly increased in the BAL
¯uid of HIV-infected persons asymptomatic or with active P. carinii pneumo-
nia, but absent in BAL ¯uid of healthy individuals ( Fraser et al., 2000). Recent
observations demonstrate that surface TNF receptors are also reduced on AM
from asymptomatic HIV-infected persons, accompanied by increased soluble
forms of the TNF receptors I and II in the cell-free BAL ¯uid of these in-
dividuals (Skolnik et al., 2000). These observations suggest that HIV infection
is associated with increased release of soluble forms of macrophage receptors.
The consequences of these changes are not completely understood, although
soluble mannose receptors may impair AM recognition of P. carinii (Fraser et
al., 2000).
Signal Transduction Pathways
AM signaling pathways are poorly understood and incompletely studied. Major
signal transduction pathways such as NF-kB/I-kB appear intact in AM from
asymptomatic HIV-infected individuals on highly active antiretroviral therapy
(HAART ) therapy and TNF-a release is comparable to healthy individuals
(Mathys et al., 2000).
SUMMARY
The mechanism(s) accounting for altered AM function remain to be estab-
lished. Investigations featuring in vitro infection of alveolar macrophages sug-
gest that HIV-1 infection is su½cient to account in part for the alterations
(Koziel et al., 1998a; Ieong et al., 2000), and may re¯ect the in¯uence of
speci®c HIV-1 gene products or alterations in vital cellular pathways mediated
by HIV-1. In the lungs of HIV-1-infected individuals, altered AM function may
also re¯ect alterations in the local alveolar microenvironment including alter-
ations in the cellular composition, and the relative concentrations of cytokines,
chemokines, and other biomodifying agents.
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