C. Elbim et al., Redox and activation status of monocytes from human immunodeficiency virus-infected patients: Relationship with viral load, J VIROLOGY, 73(6), 1999, pp. 4561-4566
Monocytes are precursors of tissue macrophages, which are major targets of
human immunodeficiency virus type 1 (HIV-1) infection. Although few blood m
onocytes are infected, their resulting activation could play a key role in
the pathogenesis of HIV disease by modulating their transendothelial migrat
ion and inducing the production of reactive oxygen species (ROS). ROS parti
cipate in chronic inflammation, HN replication, and the apoptosis of immune
system cells seen in HIV-infected subjects. Published data on monocyte act
ivation are controversial, possibly because most studies have involved mono
cytes isolated from their blood environment by various procedures that may
alter cell responses. We therefore used flow cytometry to study, in whole b
lood, the activation and redox status of monocytes from HIV infected patien
ts at different stages of the disease. We studied the expression of adhesio
n molecules, actin polymerization, and cellular levels of H2O2, Bcl-2, and
thioredoxin. Basal H2O2 production correlated with viral load and was furth
er enhanced by bacterial N-formyl peptides and endotoxin. The enhanced H2O2
production by monocytes from asymptomatic untreated patients with CD4(+) c
ell counts above 500/mu l was associated with a decrease in the levels of B
cl-2 and thioredoxin, In contrast, in patients with AIDS, Bcl-2 levels retu
rned to normal and thioredoxin levels were higher than in healthy controls.
Restoration of these antioxidant and antiapoptotic molecules might explain
, at least in part, why monocyte numbers remain relatively stable throughou
t the disease. Alterations of adhesion molecule expression and increased ac
tin polymerization could play a role in transendothelial migration of these
activated monocytes.