Mitochondrial reactive oxygen species are involved in chemoattractant-induced oxidative burst and degranulation of human neutrophils in vitro.
Activation of neutrophils is accompanied by the oxidative burst, exocytosis of various granule types (degranulation) and a delay in spontaneous apoptosis. The major source of reactive oxygen species (ROS) in human neutrophils is NADPH oxidase (NOX2), however, other sources of ROS also exist. Although the function of ROS is mainly defensive, they can also play a regulatory role in cell signaling. However, the contribution of various sources of ROS in these processes is not clear. We investigated a possible role of mitochondria-derived ROS (mtROS) in the regulation of neutrophil activation induced by chemoattractant fMLP in vitro. Using the mitochondria-targeted antioxidant SkQ1, we demonstrated that mtROS are implicated in the oxidative burst caused by NOX2 activation as well as in the exocytosis of primary (azurophil) and secondary (specific) granules. Scavenging of mtROS with SkQ1 slightly accelerated spontaneous apoptosis and significantly stimulated apoptosis of fMLP-activated neutrophils. These data indicate that mtROS play a critical role in signal transduction that mediates the major neutrophil functional responses in the process of activation.
Department Immunology, Biology Faculty; Lomonosov Moscow State University, 119998 Moscow, Russia; Institute of Immunology, FMBA, Kashirskoe Shosse 24/2, 115478, Moscow, Russia. Electronic address: nvvorobjeva@mail.ru.
Nina
N
Vorobjeva
Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia.
Anastasia
A
Prikhodko
A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.
Ivan
I
Galkin
A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.
Olga
O
Pletjushkina
A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.
Roman
R
Zinovkin
A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.
Galina
G
Sud'ina
A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.
Boris
B
Chernyak
Institute of Immunology, FMBA, Kashirskoe Shosse 24/2, 115478, Moscow, Russia.
Boris
B
Pinegin
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D002478:Cells, Cultured; D002630:Chemotactic Factors / Q000494:pharmacology*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D005089:Exocytosis; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress; D010971:Plastoquinone / Q000031:analogs & derivatives / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*
C532038:10-(6'-plastoquinonyl)decyltriphenylphosphonium; D000975:Antioxidants; D002630:Chemotactic Factors; D017382:Reactive Oxygen Species; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010971:Plastoquinone
Degranulation; Human neutrophils; Mitochondria-targeted antioxidant SkQ1; NADPH oxidase; Oxidative burst; Reactive oxygen species