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Reactive oxygen species-dependent necroptosis in Jurkat T cells induced by pathogenic free-living Naegleria fowleri.

Authors
 K.-J. SONG ; Y. S. JANG ; M. H. SHIN ; S. K. LEE ; K. A. KIM ; Y. A. LEE 
Citation
 Parasite Immunology, Vol.33(7) : 390~400, 2011 
Journal Title
 Parasite Immunology 
ISSN
 0141-9838 
Issue Date
2011
Abstract
Naegleria fowleri, a free-living amoeba, is the causative pathogen of primary amoebic meningoencephalitis in humans and experimental mice. N. fowleri is capable of destroying tissues and host cells through lytic necrosis. However, the mechanism by which N. fowleri induces host cell death is unknown. Electron microscopy indicated that incubation of Jurkat T cells with N. fowleri trophozoites induced necrotic morphology of the Jurkat T cells. N. fowleri also induced cytoskeletal protein cleavage, extensive poly (ADP-ribose) polymerase hydrolysis and lactate dehydrogenase (LDH) release. Although no activation of caspase-3 was observed in Jurkat T cells co-incubated with amoebae, intracellular reactive oxygen species (ROS) were strongly generated by NADPH oxidase (NOX). Pretreating cells with necroptosis inhibitor necrostatin-1 or NOX inhibitor diphenyleneiodonium chloride (DPI) strongly inhibited amoeba-induced ROS generation and Jurkat cell death, whereas pan-caspase inhibitor z-VAD-fmk did not. N. fowleri-derived secretory products (NfSP) strongly induced intracellular ROS generation and cell death. Necroptotic effects of NfSP were effectively inhibited by pretreating NfSP with proteinase K. Moreover, NfSP-induced LDH release and intracellular ROS accumulation were inhibited by pretreating Jurkat T cells with DPI or necrostatin-1. These results suggest that N. fowleri induces ROS-dependent necroptosis in Jurkat T cells
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/93404
DOI
10.1111/j.1365-3024.2011.01297.x
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Environmental Medical Biology
Yonsei Authors
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Link
 http://onlinelibrary.wiley.com/doi/10.1111/j.1365-3024.2011.01297.x/abstract
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