The role of phagocytes in HIV-related oxidative stress

Background: in response to a variety of stimuli, phagocytes release large q uantities of reactive oxygen species (ROS), which are essential for bacteri al killing. However, excessive ROS production not appropriately compensated by antioxidant molecules can lead to oxidative stress, which may also play an important role in pathogenesis of HIV infection. In fact, ROS participa te in chronic inflammation, HIV replication and the apoptosis of cells of t he immune system. Objective and study design: we used flow cytometry to stu dy, in whole blood, the activation and redox status of polymorphonuclear ne utrophils (PMN) and monocytes at different stages of the disease. Results: we showed that neutrophils and monocytes from HIV-infected patients spontan eously produced increased amounts of H2O2. This increased H2O2 production w as associated with alterations of adhesion molecules expression at the cell surface, which also reflected basal activation of phagocytes from the HIV- infected patients. In monocytes, basal H2O2 production correlated with vira l load. This increased ROS production was associated with changes in the ex pression of the antiapoptotic/antioxidant compounds Bcl-2 and thioredoxin a long the course of the disease. This modulation could result from a dual re gulation by oxidative stress and could explain at least in part why monocyt e numbers remain relatively stable throughout the disease. Monocytes expres sed a normal maximal capacity to produce ROS in optimal conditions of stimu lation. In contrast, after ex vivo priming with TNF alpha or IL-8, neutroph ils showed a decreased H2O2 production in response to bacterial N-formyl pe ptides. This latter impairment correlated with the decrease in CD4 + lympho cyte numbers and with IL-8 and IL-6 plasma levels. Conclusions,ls: the incr eased basal ROS production by phagocytes could participate to the oxidative injury which has been implicated in the pathophysiology of HIV infection. In addition, the decreased priming of H2O2 production by neutrophils could contribute to the increased susceptibility of HIV-infected patients to bact erial infections. (C) 2001 Elsevier Science B.V. All rights reserved.