Amplification of the inflammatory cellular redox state by human immunodeficiency virus type 1-immunosuppressive tat and gp160 proteins.
In the course of our studies on oxidative stress as a component of pathological processes in humans, we showed that microintrusion into cells with microcapillary and ultramicroelectrochemical detection could mimic many types of mechanical intrusion leading to an instant (0.1 s) and high (some femtomoles) burst release of H2O2. Specific inhibitors of NADPH enzymes seem to support the assumption that this enzyme is one of the main targets of our experiments. Also, human immunodeficiency virus type 1 (HIV-1) gp160 inhibits the cooperative response of uninfected T cells as well as Tat protein release by infected cells does. In this study, we analyzed in real time, lymphocyte per lymphocyte, the T-cell response following activation in relation to the redox state. We showed that the immunosuppressive effects of HIV-1 Tat and gp160 proteins and oxidative stress are correlated, since the native but not the inactivated Tat and gp160 proteins inhibit the cellular immune response and enhance oxidative stress. These results are consistent with a role of the membrane NADPH oxidase in the cellular response to immune activation.
Lachgar
A
A
Université Pierre et Marie Curie, Ecole Normale Supérieure, Paris, France.
Sojic
N
N
Arbault
S
S
Bruce
D
D
Sarasin
A
A
Amatore
C
C
Bizzini
B
B
Zagury
D
D
Vuillaume
M
M
D001152:Arsenicals / Q000494:pharmacology; D002455:Cell Division; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015696:Gene Products, tat / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D019302:HIV Envelope Protein gp160 / Q000276:immunology* / Q000494:pharmacology; D015497:HIV-1 / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000276:immunology* / Q000494:pharmacology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000276:immunology*; D054322:tat Gene Products, Human Immunodeficiency Virus
D001152:Arsenicals; D004791:Enzyme Inhibitors; D015696:Gene Products, tat; D019302:HIV Envelope Protein gp160; D007166:Immunosuppressive Agents; D054322:tat Gene Products, Human Immunodeficiency Virus; C029341:oxophenylarsine; D019255:NADPH Oxidases