CHARACTERISTICS OF NITRIC OXIDE-INDUCED APOPTOSIS AND ITS TARGET CELLS IN MITOGEN-STIMULATED PERIPHERAL BLOOD MONONUCLEAR CELLS FROM HIV+ SUBJECTS

The phenomenon of apoptosis observed in lymphoid cells from HIV+ subjects is an important factor contributing to their massive depletion. Several studies have identified nitric oxide (NO) as one of the molecules involved in the apoptosis phenomenon observed during HIV infection. It has been shown that HIV-derived gp120 enhances NO synthesis in cultured cells from HIV+ individuals. Therefore, we tested the potential of two nitric oxide synthase (NOS) inhibitors with different mechanisms of action as preventive agents of in vitro apoptosis, in peripheral blood mononuclear cells (PBMC) from HIV+ subjects. PBMC isolated from these patients always showed higher apoptosis levels than normal subjects, a fact that correlated with overproduction of NO and with reduction of mitochondrial transmembrane potential in these cells. We identified the CD8+ T lymphocyte sub-population as the major apoptosis target in PBMC cultures. Treatment with NO inhibitors NG-monomethyl-L-arginine (L-NMMA) and dexamethasone (DEX) inhib...