Biology Reference
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enhanced spontaneous release of superoxide anion, and increased IP-10 gene
expression by AM from HIV-infected persons (Buhl et al., 1993). The ®nding
of increased IP-10 mRNA expression, generally induced by IFN-g ( Luster and
Ravetch, 1987), suggests intraalveolar exposure to IFN-g, a recognized activa-
tor of macrophages, may account for the observed activation. Other studies
have not described increased HLA-DR expression ( Koziel et al., 1998a). The
mechanisms for the observed activated state remain to be established, but cer-
tainly in part re¯ect active pulmonary disease related to HIV-1 infection (as
many of the subjects studied were symptomatic).
Cytokine Release
The e¨ect of HIV-1 infection on the release of cytokines remains uncertain and
controversial. AM from HIV-infected persons may spontaneously release in-
creased amounts of cytokines, and may also exhibit an exaggerated response to
in vitro stimuli (Agostini et al., 1991a, 1992; Israel-Biet et al., 1991; Millar et
al., 1991; Trentin et al., 1992; Twigg et al., 1992; Sierra-Madero et al., 1994).
Although these observations may in part re¯ect active lung disease, these ®nd-
ings were also observed in certain asymptomatic individuals. TNF receptors
may be in¯uenced by HIV-1 infection, as recent observations suggest that
TNF-receptor I and TNF-receptor II are both down-regulated in AM from
asymptomatic HIV-infected persons (Skolnik et al., 2000). The pathological
consequences may in¯uence both host defense function as well as in¯uence
HIV-1 replication of infected cells.
Accessory Cell Function
Although antigen-presenting capacity of AM may be enhanced in HIV infec-
tion, and surface expression of MHC class II molecules may be increased, the
interactions of AM with mitogen-induced T lymphocytes are similar to those in
healthy individuals (Twigg and Soliman, 1994). However, the speci®c receptor-
ligand and the role of coreceptor stimulation is poorly understood. The antigen-
presenting capacity of AM from HIV-infected persons may be greater com-
pared with healthy individuals ( Twigg et al., 1989). This enhanced capacity
may in part re¯ect AM activation, although asymptomatic individuals ex-
hibited the greatest enhanced capacity. Alternatively, the enhanced antigen-
presenting capacity may re¯ect elevated levels of stimulatory cytokines such as
IL-1 and IL-6, or enhanced AM response to these cytokines.
Surfactant Regulation
AM participate in the processing of pulmonary surfactant components such
as SP-A (Hawgood and Clements, 1990). SP-A contributes to alveolar gas
exchange by lowering surface tension in the alveolar airspace, and may also
participate as a nonimmune opsonin in the innate immune response. Although
SP-A levels are elevated in the lungs of asymptomatic HIV-infected persons
