title: Mechanisms of neutrophil death in human immunodeficiency virus-infected patients: role of reactive oxygen species, caspases and map kinase pathways.
abstract: Neutrophils from human immunodeficiency virus-positive (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, mitogen activated protein kinase (MAPK) and reactive oxygen species (ROS) was analysed. Spontaneous neutrophil death is dependent upon caspase-3 but independent of caspase-8, 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 activation with neutrophil PCD in HIV-infected patients. Additionally, an increased neutrophil death was observed in HIV+ patients, following inhibition of p38 MAPK, 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.
authors.affiliation: Institute of Clinical Immunology, University of Los Andes, Merida, Venezuela.
authors.forename: S
authors.initials: S
authors.lastname: Salmen
authors.forename: H
authors.initials: H
authors.lastname: Montes
authors.forename: A
authors.initials: A
authors.lastname: Soyano
authors.forename: D
authors.initials: D
authors.lastname: Hernández
authors.forename: L
authors.initials: L
authors.lastname: Berrueta
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis; D053148:Caspase 3 / Q000502:physiology; D020169:Caspases / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D015658:HIV Infections / Q000201:enzymology / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000473:pathology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D013481:Superoxides; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D020169:Caspases