Trichomonas vaginalis: reactive oxygen species mediates caspase-3 dependent apoptosis of human neutrophils.
There are many neutrophils in the vaginal discharge from women infected with Trichomonas vaginalis. The aim of our study was to determine whether human neutrophil apoptosis may be regulated by reactive oxygen species (ROS) in response to trichomonads infection. Incubation of human neutrophils with live trichomonads caused marked receptor shedding of CD16, decrease of mitochondrial membrane potential (MMP) and caspase-3 activation in human neutrophils. These proapoptotic effects of T. vaginalis on neutrophils were inhibited by pretreatment of neutrophils with an inhibitor of NADPH oxidase, diphenyleneiodonium chloride (DPI), suggesting an important role of intracellular ROS accumulation in T. vaginalis-triggered apoptosis. Indeed, large amounts of ROS levels were detected in neutrophils incubated with live trichomonads, and were also effectively inhibited by DPI. However, pan-caspase inhibitor z-VAD-fmk or caspase-3 inhibitor z-DEVD-fmk did not affect T. vaginalis-induced ROS generation in neutrophils. These results suggest that ROS-dependent caspase-3 activation plays an important role in apoptosis of human neutrophils induced by T. vaginalis.
Song
Hyun-Ouk
HO
Department of Parasitology, Brain Korea 21, Hanyang University College of Medicine, 17 Haengdang-dong, Seongdong-gu, Seoul 133-791, Republic of Korea.
Shin
Myeong-Heon
MH
Ahn
Myoung-Hee
MH
Min
Duk-Young
DY
Kim
Yong-Seok
YS
Ryu
Jae-Sook
JS
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009861:Onium Compounds / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017452:Receptors, IgG / Q000378:metabolism; D014246:Trichomonas vaginalis / Q000378:metabolism*
D004791:Enzyme Inhibitors; D009861:Onium Compounds; D017382:Reactive Oxygen Species; D017452:Receptors, IgG; C007517:diphenyleneiodonium; D019255:NADPH Oxidases; D053148:Caspase 3