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Monochloramine enhances Fas (APO‐1/CD95)‐induced apoptosis in Jurkat T cells
Author(s) -
Ogino Tetsuya,
Ma Yuxiang,
Than Tin Aung,
Omori Masako,
Okada Shigeru
Publication year - 2000
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.67.1.46
Subject(s) - jurkat cells , apoptosis , biology , fas receptor , microbiology and biotechnology , cancer research , programmed cell death , immunology , immune system , t cell , genetics
Monochloramine derivatives are physiological oxidants produced by activated neutrophils. We report the effects of chemically prepared monochloramine (NH 2 Cl) on Fas‐induced apoptosis in Jurkat T cells. When the cells were pretreated with NH 2 Cl (20–70 μM), subsequent addition of apoptosis‐inducing anti‐Fas antibody resulted in a synergistic enhancement of apoptosis. Treatment of NH 2 Cl (50–70 μM) alone resulted in a slight but definite apoptosis. Caspase activities, as measured by DEVD and IETD cleavage activities, were also elevated synergistically by NH 2 Cl + anti‐Fas antibody stimulation. Moreover, a broad caspase inhibitor, Z‐VAD‐fmk, almost completely inhibited the apoptosis induced by NH 2 Cl and/or anti‐Fas antibody. Fas expression on the Jurkat cell surface was not affected by the NH 2 Cl treatment. After 3 h of NH 2 Cl treatment, when the apoptosis was beginning to increase, the cells showed cytochrome c release from mitochondria, proteolytic activation of caspase 9, and poly (ADP‐ribose) polymerase cleavage, regardless of Fas stimulation. Z‐VAD‐fmk almost completely inhibited this poly (ADP‐ribose) polymerase cleavage, but not cytochrome c release. By contrast, Fas stimulation alone resulted in neither cytochrome c release nor caspase 9 activation at 3 h, and the increase in the DEVD cleavage activity and apoptosis became evident at later time points. These results suggested that NH 2 Cl enhanced Fas‐induced apoptosis through the cytochrome c release and caspase 9 activation at the early stage of apoptosis. Chloramines derived from acute inflammation may modify immune reactions, such as cell‐mediated cytotoxicity and some autoimmune diseases, by the enhancement of Fas‐induced apoptosis. J. Leukoc. Biol. 67: 46–52; 2000.