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Mitochondria Alterations And Dramatic Tendency To Undergo Apoptosis In Peripheral Blood Lymphocytes During Acute HIV Syndrome

A. Cossarizza, C. Mussini, N. Mongiardo, V. Borghi, A. Sabbatini, B. De Rienzo, C. Franceschi
Published 1997 · Medicine

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Objective:To study alterations of mitochondrial membrane potential (Δψ) and the propensity to undergo apoptosis in peripheral blood lymphocytes (PBL) from subjects with acute HIV syndrome; and to evaluate possible modulations of these phenomena by antioxidants that can be used in therapy, such as N-acetyl-cysteine (NAC), nicotinamide (NAM), or L-acetyl-carnitine (LAC). Methods:Mitochondrial function and the tendency of PBL to undergo spontaneous apoptosis were studied on freshly collected PBL from patients with symptomatic, acute HIV-1 primary infection, which were cultured for different durations in the presence or absence of NAC, NAM or LAC. By a cytofluorimetric method allowing analysis of Δψ in intact cells, we studied the function of these organelles under the different conditions. PBL apoptosis was evaluated by the classic cytofluorimetric method of propidium iodide staining, capable of revealing the typical DNA hypodiploid peak. Results:Significant Δψ alterations and tendency to undergo apoptosis were present in PBL from the subjects we studied. Indeed, when cultured even for a few hours in the absence of any stimulus, a consistent number of cells died. However, the presence of even different levels of NAC, NAM or LAC was able to rescue most of them from apoptosis. Both a fall in Δψ and apoptosis were evident in PBL collected in the earliest phases of the syndrome (before seroconversion), and changed significantly after a few days. A significant correlation was found between spontaneous apoptosis and tumour necrosis factor (TNF)-α or p24 plasma levels, as well as between apoptosis and the percentages of circulating CD4+ or CD8+ T cells. Conclusions:PBL from patients with acute HIV syndrome are characterized by both significant mitochondrial alterations and a dramatic tendency to undergo apoptosis. The use of NAC, NAM or LAC seems to rescue cells through a protective effect on mitochondria, a well-known target for the action of TNF-α and for reactive oxygen species, the production of which is strongly induced by this cytokine. Thus, our data could provide the rationale for the use of such agents in addition to antiviral drugs in primary infection.
This paper references
10.1073/PNAS.87.2.782
Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression.
G. Poli (1990)
Tumor necrosis factor alpha functions in an autocrine manner in the induction of human immunodeficiency virus expression.
(1990)
10.1016/0891-5849(95)00047-2
The role of oxidative stress in HIV disease.
G. W. Pace (1995)
10.1056/NEJM199508173330702
A controlled trial of zidovudine in primary human immunodeficiency virus infection.
S. Kinloch-de Loës (1995)
10.1084/JEM.175.2.331
Activation-induced death by apoptosis in CD4+ T cells from human immunodeficiency virus-infected asymptomatic individuals
H. Groux (1992)
10.1126/SCIENCE.7716549
Induction of apoptosis in uninfected lymphocytes by HIV-1 Tat protein.
C. Li (1995)
10.1097/00002030-199112000-00001
Cytokines and HIV infection: is AIDS a tumor necrosis factor disease?
T. Matsuyama (1991)
Anergy and apoptosis in CD8+ T cells from HIV-infected persons.
D. Lewis (1994)
10.1016/0022-1759(95)00140-6
The use of non-radioactive chromium as an alternative to 51Cr in NK assay.
P. Borella (1995)
10.1097/00002030-199111000-00006
Serum interleukin-6 concentrations are elevated and associated with elevated tumor necrosis factor-α and immunoglobulin G and A concentrations in children with HIV infection
J. Rautonen (1991)
10.1126/SCIENCE.3277274
The human immunodeficiency virus: infectivity and mechanisms of pathogenesis.
A. S. Fauci (1988)
10.1016/S0140-6736(85)91205-X
ACUTE AIDS RETROVIRUS INFECTION: Definition of a Clinical Illness Associated with Seroconversion
D. Cooper (1985)
10.1021/BI00232A015
J-aggregate formation of a carbocyanine as a quantitative fluorescent indicator of membrane potential.
M. Reers (1991)
Mitochondria as targets for the protective effects of heat shock against oxidative injury
BS Polla (1996)
Practical Flow Cytometry (3rd Edn)
HM Shapiro (1995)
Massive activation of immune cells with an intact T cell repertoire in acute HIV syndrome
A Cossarizza (1995)
10.1056/NEJM199104043241404
High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection.
S. J. Clark (1991)
with fluorescent dyes
HM Shapiro (1984)
10.1080/09553009014551621
Recovery of human lymphocytes damaged with gamma-radiation or enzymatically produced oxygen radicals: different effects of poly(ADP-ribosyl)polymerase inhibitors.
M. Marini (1990)
10.1016/0014-5793(93)81043-Y
N‐Acetylcysteine inhibits apoptosis and decreases viral particles in HIV‐chronically infected U937 cells
W. Malorni (1993)
10.1056/NEJM199508173330710
Time to hit HIV, early and hard.
D. Ho (1995)
Early progression to AIDS following primary HIV infection.
C. Pedersen (1989)
Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone.
K. Clouse (1989)
The role of poly ( ADP - ribose ) synthesis in toxicity and repair of DNA dam
JE Cleaver (1988)
10.1016/0047-6374(89)90005-5
Effect of aging and acetyl-l-carnitine on energetic and cholinergic metabolism in rat brain regions
D. Curti (1989)
10.1182/BLOOD.V86.7.2481.2481
Mitochondrial dysfunctions in circulating T lymphocytes from human immunodeficiency virus-1 carriers.
A. Macho (1995)
10.1097/00002030-199105000-00004
Inhibition of HIV‐1 replication and NF-x B activity by cysteine and cysteine derivatives
S. Mihm (1991)
10.1182/BLOOD.V82.11.3392.BLOODJOURNAL82113392
Accelerated apoptosis in peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus type-1 infected patients and in CD4 cross-linked PBMCs from normal individuals.
N. Oyaizu (1993)
10.1073/PNAS.88.9.3671
Intracellular heterogeneity in mitochondrial membrane potentials revealed by a J-aggregate-forming lipophilic cation JC-1.
S. Smiley (1991)
a tumor necrosis factor disease ?
WL Farrar (1991)
10.1080/13510002.1994.11746957
N-acetylcysteine prevents TNF-induced mitochondrial damage, apoptosis and viral particle production in HIV-infected U937 cells.
W. Malorni (1994)
10.1006/BBRC.1994.1260
Cell death protection by 3-aminobenzamide and other poly(ADP-ribose)polymerase inhibitors: different effects on human natural killer and lymphokine activated killer cell activities.
D. Monti (1994)
10.1515/BCHM3.1989.370.1.101
Low concentrations of acid-soluble thiol (cysteine) in the blood plasma of HIV-1-infected patients.
H. Eck (1989)
Programmed cell death of T cells in HIV-1 infection
L Meyaard (1992)
Low concentration of soluble thiol (cysteine) in the blood plasma of HIV-1 infected patients
H-P Eck (1989)
10.1097/00002030-199010000-00008
Immunological changes in primary HIV‐1 infection
H. Gaines (1990)
10.1016/0952-7915(95)80088-3
The immunology of primary HIV infection: which immune responses control HIV replication?
J. Safrit (1995)
10.1093/ajcn/55.6.1208S
Apoptosis--programmed cell death: a role in the aging process?
D. Monti (1992)
Cossarizza A: Down syndrome, centenarians and oxidative stress: the rationale for the use of nicotinamide and carnitines as anti-aging substances
C Franceschi (1993)
10.1097/00002030-199101000-00001
Primary HIV infection: host responses and intervention strategies.
B. Tindall (1991)
10.1016/0014-5793(95)01431-4
Control of apoptosis by the cellular ATP level
C. Richter (1996)
10.1097/00002030-199006000-00005
T-cell subset alterations and lymphocyte responsiveness to mitogens and antigen during severe primary infection with HIV: a case series of seven consecutive HIV seroconverters.
C. Pedersen (1990)
10.1097/00002030-198911000-00009
Serum thymidine kinase--a marker of bone marrow toxicity during treatment with zidovudine.
C. Pedersen (1989)
10.1126/SCIENCE.1352911
Programmed death of T cells in HIV-1 infection.
L. Meyaard (1992)
Serum interleukin-6 concentrations are elevated and associ-ated with elevated tumor necrosis factor-α and immunoglobulin G and A concentrations in children with HIV infection
J Rautonen (1991)
Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. Evidence for the involvement of mitochondrial radical generation.
K. Schulze-Osthoff (1992)
10.1016/1043-4666(91)90479-W
Cytokine regulation of human immunodeficiency virus expression.
W. Farrar (1991)
Programmed cell death and AIDS: significance, perspectives and unanswered questions.
J. C. Ameisen (1995)
10.1038/bjc.1972.33
Apoptosis: A Basic Biological Phenomenon with Wide-ranging Implications in Tissue Kinetics
J. Kerr (1972)
10.1056/NEJM199104043241405
Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection.
E. Daar (1991)
10.1038/NM0295-118
Apoptosis in HIV infection
G. Pantaleo (1995)
10.1073/PNAS.87.12.4884
Cytokine-stimulated human immunodeficiency virus replication is inhibited by N-acetyl-L-cysteine.
M. Roederer (1990)
following primary HIV infection [ letter ]
H Gaines (1989)
Accelerated apoptosis in PBMCs from HIV-1 infected patients and in CD4 cross-linked PBMCs from normal individuals
N Oyaizu (1993)
De Bels F: Programmed cell death and AIDS: significance, perspectives and unanswered questions
J C Ameisen (1995)
10.1182/BLOOD.V80.2.452.BLOODJOURNAL802452
Apoptotic cell death of primed CD45RO+ T lymphocytes in Epstein-Barr virus-induced infectious mononucleosis.
T. Uehara (1992)
Transient levels of viremia in patients with primary human immunodeficiency virus type 1 infection
ES Daar (1991)
Infection with HIV is associated with elevated IL-6 levels and production.
E. Breen (1990)
10.1073/PNAS.93.13.6458
Mitochondria are selective targets for the protective effects of heat shock against oxidative injury.
B. Polla (1996)
10.1001/JAMA.1987.03400090080038
Diagnosis of human immunodeficiency virus infection in seronegative homosexuals presenting with an acute viral syndrome.
H. Kessler (1987)
10.1126/SCIENCE.3399881
HIV causes AIDS.
W. Blattner (1988)
Boveris A: Hydroperoxide metabolism in mammalian organs
B Chance (1979)
10.1172/JCI117105
Programmed death of T cells in human immunodeficiency virus infection. No correlation with progression to disease.
L. Meyaard (1994)
10.1056/NEJM199301283280402
Early treatment of acute biliary pancreatitis by endoscopic papillotomy.
S. Fan (1993)
10.1006/BBRC.1993.2438
A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1).
A. Cossarizza (1993)
10.1042/BJ2890587
Tumour necrosis factor-α induces superoxide anion generation in mitochondria of L929 cells
T. Hennet (1993)
10.1038/NM0295-129
Apoptosis occurs predominantly in bystander cells and not in productively infected cells of HIV- and SIV-infected lymph nodes
T. Finkel (1995)
Temin HM: HIV causes AIDS
W Blattner (1988)
10.1016/0092-8674(84)90530-0
Localization of endoplasmic reticulum in living and glutaraldehyde-fixed cells with fluorescent dyes
M. Terasaki (1984)
10.1016/1043-6618(95)86819-4
Evidence for dissimilar mechanisms of enhancement of inorganic and organic hydroperoxide cytotoxicity by L-histidine.
A. Guidarelli (1995)
10.1016/0022-1759(91)90198-O
A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry.
I. Nicoletti (1991)
10.1006/EXCR.1995.1311
Protective effect of N-acetylcysteine in tumor necrosis factor-alpha-induced apoptosis in U937 cells: the role of mitochondria.
A. Cossarizza (1995)
Spectroscopic study on the J-aggregate of cyanine dyes. I. Spectral changes of UV bands concerned with J-aggregate formation
H Hada (1977)
10.1128/AAC.39.12.2807
Thalidomide inhibits lipoarabinomannan-induced upregulation of human immunodeficiency virus expression.
P. Peterson (1995)
10.1016/0167-5699(91)90092-8
Cell dysfunction and depletion in AIDS: the programmed cell death hypothesis.
J. C. Ameisen (1991)
10.1056/NEJM199301283280419
Acute immunosuppression with HIV seroconversion.
K. Gupta (1993)
10.1006/EXCR.1995.1131
Sendai virus and herpes virus type 1 induce apoptosis in human peripheral blood mononuclear cells.
F. Tropea (1995)
10.1006/EXCR.1994.1264
Mitochondrial modifications during rat thymocyte apoptosis: a study at the single cell level.
A. Cossarizza (1994)
10.1111/j.1749-6632.1988.tb22377.x
Effect of ADP‐Ribosyl Transferase Inhibitors on the Survival of Human Lymphocytes after Exposure to Different DNA‐Damaging Agents a
C. Franceschi (1988)
10.1016/0042-6822(91)90554-O
The cytopathic effect of HIV is associated with apoptosis.
A. Laurent-Crawford (1991)
10.1016/0167-5699(83)90015-4
This letter was sent to Dr Johnstone.
A. Johnstone (1983)
10.1006/BBRC.1995.2315
Mitochondrial mass and membrane potential in coelomocytes from the earthworm Eisenia foetida: studies with fluorescent probes in single intact cells.
A. Cossarizza (1995)
10.1089/AID.1993.9.761
Membrane expression of HIV envelope glycoproteins triggers apoptosis in CD4 cells.
A. Laurent-Crawford (1993)
10.1152/PHYSREV.1979.59.3.527
Hydroperoxide metabolism in mammalian organs.
B. Chance (1979)
10.1084/JEM.172.1.151
Interleukin 6 induces human immunodeficiency virus expression in infected monocytic cells alone and in synergy with tumor necrosis factor alpha by transcriptional and post-transcriptional mechanisms
G. Poli (1990)
10.1093/INFDIS/172.1.105
Massive activation of immune cells with an intact T cell repertoire in acute human immunodeficiency virus syndrome.
A. Cossarizza (1995)
10.1097/00002030-199506000-00003
Lack of selective Vβ deletion in CD4+ or CD8+ T lymphocytes and functional integrity of T‐cell repertoire during acute HIV syndrome
A. Cossarizza (1995)
10.1016/0163-7258(85)90026-9
The role of poly(ADP-ribose) synthesis in toxicity and repair of DNA damage.
J. Cleaver (1985)
How HIV causes AIDS.
M. A. Spartalis (1995)
10.1097/00002030-198901000-00010
Isolation of HIV-1 from small volumes of heparinized whole blood.
C. Pedersen (1989)
A rapid simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry
I Nicoletti (1991)
Down syndrome , centenarians and oxidative stress : the rationale for the use of nicotinamide and carnitines as anti - aging substances
C Franceschi (1989)
10.1136/bmj.309.6968.1535
Does symptomatic primary HIV-1 infection accelerate progression to CDC stage IV disease, CD4 count below 200 × 106/l, AIDS, and death from AIDS?
S. Lindback (1994)
Tumor necrosis factor-mediated cytotoxicity involves ADP-ribosylation.
S. Agarwal (1988)
10.1097/00002030-199301000-00020
Administration of zidovudine during primary HIV-1 infection may be associated with a less vigorous immune response.
B. Tindall (1993)
10.1016/S0140-6736(89)91909-0
SYSTEMIC GLUTATHIONE DEFICIENCY IN SYMPTOM-FREE HIV-SEROPOSITIVE INDIVIDUALS
R. Buhl (1989)



This paper is referenced by
10.1086/338564
Mitochondrial functionality and mitochondrial DNA content in lymphocytes of vertically infected human immunodeficiency virus-positive children with highly active antiretroviral therapy-related lipodystrophy.
A. Cossarizza (2002)
10.1182/BLOOD.V98.10.3066
Activation of apoptosis pathways in peripheral blood lymphocytes by in vivo chemotherapy.
K. Stahnke (2001)
10.1201/9781420038156.CH17
Nonapoptotic HIV-Induced T Cell Death
Matthew Smith-Raska (2005)
EDITORIAL REVIEW: Role of CD38 in HIV-1 infection: an epiphenomenon of T-cell activation or an active player in virus/host interactions?
Andrea Savarinoa ()
Early changes in intramitochondrial cardiolipin distribution during apoptosis.
M. G. Garcia Fernandez (2002)
10.1006/EXCR.2000.4901
During apoptosis of HL-60 and U-937 cells caspases are activated independently of dissipation of mitochondrial electrochemical potential.
X. Li (2000)
10.1096/fj.00-0336fje
HIV induces lymphocyte apoptosis by a p53‐initiated, mitochondrial‐mediated mechanism
D. Genini (2001)
10.1002/JMV.20410
Depleted skeletal muscle mitochondrial DNA, hyperlactatemia, and decreased oxidative capacity in HIV‐infected patients on highly active antiretroviral therapy
S. B. Haugaard (2005)
Untersuchung des mitochondrialen Membranpotentials und der Apoptoserate peripherer mononukleärer Blutzellen HIV-positiver, bisher nicht antiretroviral behandelter Patienten
J. Bogner (2008)
10.1111/J.1574-695X.2002.TB00544.X
Mitochondrial alterations precede Bordetella pertussis-induced apoptosis.
M. Bachelet (2002)
IMMUNE ACTIVATION AND CIGARETTE SMOKE EXPOSURE AS POTENTIAL DETERMINANTS OF FAILURE OF HAART IN THE SETTING OF MOTHER-TO- CHILD TRANSMISSION.
T. G. Makhubele (2015)
10.2741/3535
Death of effector memory T cells characterizes AIDS.
Laforge Mireille (2009)
10.1101/2020.03.06.978791
Long-term T cell fitness and proliferation is driven by AMPK-dependent regulation of oxygen reactive species
Anouk Lepez (2020)
10.1053/HUPA.2000.19293
HIV-1 and its causal relationship to immunosuppression and nervous system disease in AIDS: a review.
A. Sotrel (2000)
HIV-1 subtype B and C GP120-mediated apoptosis of bystander CD4+ T lymphocytes
Natasha Camilla Pillay (2012)
10.1016/J.LFS.2003.10.021
Secoisolariciresinol and isotaxiresinol inhibit tumor necrosis factor-alpha-dependent hepatic apoptosis in mice.
A. Banskota (2004)
10.1016/J.MOLSTRUC.2012.04.057
Ten metal complexes of vitamin B3/niacin: Spectroscopic, thermal, antibacterial, antifungal, cytotoxicity and antitumor studies of Mn(II), Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Pd(II), Cd(II), Pt(IV) and Au(III) complexes
F. A. Al-Saif (2012)
10.1016/S0003-9861(02)00342-9
L-Carnitine inhibits cisplatin-induced injury of the kidney and small intestine.
B. Chang (2002)
10.1097/01.qai.0000214809.83218.88
Adverse Effects of Antiretroviral Drugs on HIV-1-Infected and -Uninfected Human Monocyte-Derived Macrophages
R. Azzam (2006)
10.1182/BLOOD.V91.10.3817.3817_3817_3824
Effect of L-carnitine on human immunodeficiency virus-1 infection-associated apoptosis: a pilot study.
S. Moretti (1998)
10.1038/sj.cdd.4400305
Phenotypic characteristics and tendency to apoptosis of peripheral blood mononuclear cells from HIV+ long term non progressors
C. Franceschi (1997)
10.1016/j.imlet.2014.01.008
Persistent inflammation in HIV infection: established concepts, new perspectives.
M. Nasi (2014)
10.1517/14622416.5.6.643
Pharmacogenetics of antiretroviral therapy: genetic variation of response and toxicity.
A. Martin (2004)
10.1097/00126334-200309010-00004
Factors Associated With Mitochondrial Dysfunction in Circulating Peripheral Blood Lymphocytes From HIV-Infected People
Rosa Polo (2003)
10.1002/0471142956.cy0732s72
Uncompensated Polychromatic Analysis of Mitochondrial Membrane Potential Using JC‐1 and Multilaser Excitation
S. de Biasi (2015)
10.1016/S0091-679X(01)63025-5
Chapter 21 Analysis of mitochondria during cell death
A. Cossarizza (2001)
10.1086/423176
Mitochondrial effects of HIV infection on the peripheral blood mononuclear cells of HIV-infected patients who were never treated with antiretrovirals.
Ó. Miró (2004)
10.1300/J128V02N02_07
Reduction of glutamate levels in HIV-infected subjects treated with acetylcarnitine.
G. Famularo (1999)
10.4049/jimmunol.164.8.3950
Cutting Edge: Increased Expression of Bcl-2 in Antigen-Specific Memory CD8+ T Cells1
J. M. Grayson (2000)
10.1097/00002030-200006160-00004
Role of CD38 in HIV-1 infection: an epiphenomenon of T-cell activation or an active player in virus/host interactions?
A. Savarino (2000)
10.1038/sj.cdd.4401595
Apoptosis of HIV-specific CD8+ T cells: an HIV evasion strategy
C. Petrovas (2005)
10.1016/J.MITO.2004.06.010
HIV-1 triggers mitochondrion death.
D. Arnoult (2004)
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