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Related Experiment Videos

Protease inhibitors stimulate hematopoiesis and decrease apoptosis and ICE expression in CD34(+) cells.

E M Sloand1, J Maciejewski, P Kumar

  • 1National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892-2490, USA.

Blood
|October 7, 2000
PubMed
Summary

Protease inhibitors, used in highly active antiretroviral therapy, may improve hematopoietic function in HIV patients by blocking apoptosis. This effect is independent of their antiviral activity, offering a new therapeutic avenue.

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Area of Science:

  • Hematology
  • Virology
  • Immunology

Background:

  • Highly active retroviral therapy (HAART) has decreased cytopenia in HIV patients.
  • Protease inhibitors (PIs) affect HIV replication and cellular functions.
  • Ritonavir was previously shown to inhibit caspase-1 in CD4(+) cells.

Purpose of the Study:

  • To investigate the hypothesis that PIs improve hematopoietic function through direct effects on bone marrow progenitor cells.
  • To determine if PIs can overcome the inhibition of hematopoiesis in HIV-infected individuals.

Main Methods:

  • Methylcellulose cultures of bone marrow cells from HIV-infected patients and controls were treated with ritonavir.
  • Cultures of CD34(+) cells were analyzed for apoptosis in the presence of ritonavir.

Related Experiment Videos

  • A synthetic caspase-1 inhibitor was used to assess its effect on apoptosis and colony formation.

    • Main Results:

    • Ritonavir significantly increased colony formation in bone marrow cells from both controls and HIV-infected patients.
    • Ritonavir markedly decreased apoptosis in CD34(+) cells from HIV-infected individuals.
    • A caspase-1 inhibitor also decreased apoptosis and enhanced progenitor cell colony formation.

    Conclusions:

    • HIV protease inhibitors may improve hematopoiesis by blocking the caspase-dependent apoptotic pathway.
    • This beneficial effect on hematopoiesis is independent of the antiviral activity of protease inhibitors.
    • Protease inhibitors offer a potential strategy to overcome hematopoiesis inhibition in HIV infection.