Critical role of nitric oxide during the apoptosis of peripheral blood leukocytes from patients with AIDS

Background: Highly active antiretroviral therapies (HAART) increase the CD4 (+) cell count, but complete normalization of this parameter has not been o btained in some patients. As oxidative stress plays an important role durin g human immunodeficiency virus type 1 (HIV-1)-associated dementia and lymph ocyte apoptosis, we asked whether the nitric ox ide (NO) pathway plays a ro le in the in vitro survival of peripheral blood mononuclear cells (PBMC) fr om HIV-1(+) patients and how it correlates with peripheral CD4(+) cell leve ls. Materials and Methods: PBMC were isolated from patients with AIDS and assay ed for apoptosis and proliferation in the presence of various chemicals, in cluding agonists or antagonists of the NO path-way. Data were then compared with several in vivo parameters from the same patients. Results: Apoptosis of PBMC in the presence of exogenous NO is significantly higher in patients with low peripheral CD4(+) cell levels than in patients with high CD4(+) cell numbers or seronegative individuals. In addition, en dogenous NO inhibition rescues cells from apoptosis in AIDS patients with l ow circulating CD4(+) cell numbers and helps recovery of the T cell prolife rative response. NO-mediated apoptosis does not require cGMP but involves p eroxynitrite generation, PARP activation, and NAD(+) depletion. Conclusions: Taken together, the data suggest the involvement of NO during the apoptosis and functional impairment of lymphocytes in patients with AID S.