Redox and activation status of monocytes from human immunodeficiency virus-infected patients: Relationship with viral load

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.