MECHANISMS OF NEUTROPHIL DEATH IN HIV INFECTED PATIENTS: ROLE OF ROS, CASPASES AND MAP KINASES PATHWAYS (46.14)

Abstract

Abstract Neutrophils from HIV+ patients have an increased susceptibility to undergo programmed cell death (PCD), which could explain neutropenia during advanced disease. In this work, key steps of PCD have been evaluated in neutrophils from HIV+ patients. The role of caspase-3, caspase-8, MAPK and ROS, were analyzed. Spontaneous neutrophil death is caspase-3 but no caspase-8 dependent, suggesting that the intrinsic pathway is involved as a pathogenic mechanism of PCD. Inhibition of ROS decreased spontaneous PCD and caspase-3 hydrolysis, connecting oxidative stress and Caspase-3 within neutrophils PCD in HIV infected patients. An increased constitutive phosphorylation of p38 MAPK, associated to increased neutrophils death in HIV+ patients, following inhibition of this kinase, was observed, suggesting a role for p38 MAPK in cell survival during the disease. We conclude that oxidative stress secondary to HIV infection can accelerate neutrophil death.