Mitochondrial membrane potential and apoptosis of blood mononuclear cells in untreated HIV-1 infected patients.
OBJECTIVE
Infection with HIV leads to progressive CD4 T-cell loss, resulting in AIDS. Apoptosis is the main mechanism for the loss of infected and bystander cells, but the complex interacting factors inducing and inhibiting apoptosis are not fully understood. Mitochondrial dysfunction is a pivotal step of the apoptotic cascade and can result in reduced mitochondrial membrane potential.


METHODS
The mitochondrial membrane potential of peripheral blood mononuclear cells (PBMC) was measured by flow cytometry using the dye JC-1 (Molecular Probes Inc). Apoptotic cells were identified using the Annexin V assay (Becton Dickinson GmbH).


RESULTS
The mitochondrial membrane potential of PBMC was significantly decreased and apoptotic cell rate was increased in HIV-infected therapy-naïve patients compared with HIV-negative controls. There was a highly significant correlation between the mitochondrial membrane potential and the rate of apoptosis. CD4 cell count was correlated negatively to the apoptotic rate and positively to the mitochondrial membrane potential.


CONCLUSIONS
The JC-1 assay is a sensitive tool to detect changes of mitochondrial membrane potential associated with apoptosis in HIV-infected therapy-naïve patients. We could show in vivo that a reduction of mitochondrial membrane potential is correlated to apoptosis of PBMC, CD4 cell count and HIV viral load during HIV infection.
Sternfeld
Thomas
T
II Medizinische Klinik und Poliklinik, Infektionsambulanz, Klinikum rechts der Isar, Technische Universität München, Munich, Germany. thomas.sternfeld@lrz.tum.de
Tischleder
A
A
Schuster
M
M
Bogner
J R
JR
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000328:Adult; D017209:Apoptosis; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000502:physiology*; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000097:blood / Q000276:immunology / Q000503:physiopathology* / Q000821:virology; D011446:Prospective Studies; D013194:Staining and Labeling; D019562:Viral Load