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 monocytes are infected, their resulting activation could play a key role in the pathogenesis of HIV disease by modulating their transendothelial migration and inducing the production of reactive oxygen species (ROS). ROS participate in chronic inflammation, HIV replication, and the apoptosis of immune system cells seen in HIV-infected subjects. Published data on monocyte activation are controversial, possibly because most studies have involved monocytes isolated from their blood environment by various procedures that may alter cell responses. We therefore used flow cytometry to study, in whole blood, the activation and redox status of monocytes from HIV-infected patients at different stages of the disease. We studied the expression of adhesion molecules, actin polymerization, and cellular levels of H2O2, Bcl-2, and thioredoxin. Basal H2O2 production correlated with viral load and was further enhanced by bacterial N-formyl peptides and endotoxin. The enhanced H2O2 production by monocytes from asymptomatic untreated patients with CD4(+) cell counts above 500/microliter was associated with a decrease in the levels of Bcl-2 and thioredoxin. In contrast, in patients with AIDS, Bcl-2 levels returned 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 throughout the disease. Alterations of adhesion molecule expression and increased actin polymerization could play a role in transendothelial migration of these activated monocytes.
Elbim
C
C
INSERM U 479 and Service d'Immunologie et d'Hématologie, CHU Xavier Bichat, Paris, France.
Pillet
S
S
Prevost
M H
MH
Preira
A
A
Girard
P M
PM
Rogine
N
N
Matusani
H
H
Hakim
J
J
Israel
N
N
Gougerot-Pocidalo
M A
MA
D000328:Adult; D004268:DNA-Binding Proteins / Q000032:analysis; D029721:Drosophila Proteins; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000821:virology; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D010084:Oxidation-Reduction; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006684:HLA-DR Antigens; D016177:Macrophage-1 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D014157:Transcription Factors; C063460:Trl protein, Drosophila; D006861:Hydrogen Peroxide