Superoxide prevents nitric oxide-mediated suppression of helper T lymphocytes: Decreased autoimmune encephalomyelitis in nicotinamide adenine dinucleotide phosphate oxidase knockout mice

被引:77
作者
van der Veen, RC
Dietlin, TA
Hofman, FM
Pen, L
Segal, BH
Holland, SM
机构
[1] Univ So Calif, Sch Med, Dept Neurol, Los Angeles, CA 90033 USA
[2] Univ So Calif, Sch Med, Dept Pathol, Los Angeles, CA 90033 USA
[3] NIAID, Host Def Lab, Bethesda, MD 20892 USA
关键词
D O I
10.4049/jimmunol.164.10.5177
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
NO, which suppresses T cell proliferation, may be inactivated by superoxide (O-2(-)) due to their strong mutual affinity. To examine this possibility, preactivated Th clones were cocultured with stimulated macrophages. PMA neutralized the inhibitory activity of NO, which aas dependent on extracellular O-2(-) production. In contrast, macrophages from p47(phox -/-) (pKO) mice, which lack functional NADPH oxidase, retained their NO-dependent inhibition of T cell proliferation upon stimulation with PMA, indicating that NADPH oxidase is the major source of NO-inactivating O-2(-) in this system. To examine the NO-O-2(-) interaction in vivo, the role of NADPH oxidase in experimental autoimmune encephalomyelitis was studied in pKO mice. No clinical or histological signs were observed in the pKO mice. Neither a bias in Th subsets nor a reduced intensity of T cell responses could account for the disease resistance. Although spleen cells from pKO mice proliferated poorly in response to the immunogen, inhibition of NO synthase uncovered a normal proliferative response, These results indicate that NO activity may play a critical role in T cell responses in pKO mite and that in normal spleens inhibition of T cell proliferation by NO may be prevented by simultaneous NADPH oxidase activity.
引用
收藏
页码:5177 / 5183
页数:7
相关论文
共 46 条
[1]  
ALBINA JE, 1991, J IMMUNOL, V147, P144
[2]   Activation of the inducible form of nitric oxide synthase in the brains of patients with multiple sclerosis [J].
Bagasra, O ;
Michaels, FH ;
Zheng, YM ;
Bobroski, LE ;
Spitsin, SV ;
Fu, ZF ;
Tawadros, R ;
Koprowski, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (26) :12041-12045
[3]   EXTENSIVE NITRATION OF PROTEIN TYROSINES IN HUMAN ATHEROSCLEROSIS DETECTED BY IMMUNOHISTOCHEMISTRY [J].
BECKMANN, JS ;
YE, YZ ;
ANDERSON, PG ;
CHEN, J ;
ACCAVITTI, MA ;
TARPEY, MM ;
WHITE, CR ;
BECKMAN, JS .
BIOLOGICAL CHEMISTRY HOPPE-SEYLER, 1994, 375 (02) :81-88
[4]   INDUCTION OF NITRIC-OXIDE SYNTHASE IN DEMYELINATING REGIONS OF MULTIPLE-SCLEROSIS BRAINS [J].
BO, L ;
DAWSON, TM ;
WESSELINGH, S ;
MORK, S ;
CHOI, S ;
KONG, PA ;
HANLEY, D ;
TRAPP, BD .
ANNALS OF NEUROLOGY, 1994, 36 (05) :778-786
[5]  
Brito C, 1999, J IMMUNOL, V162, P3356
[6]   NITRIC-OXIDE, AN ENDOTHELIAL-CELL RELAXATION FACTOR, INHIBITS NEUTROPHIL SUPEROXIDE ANION PRODUCTION VIA A DIRECT ACTION ON THE NADPH OXIDASE [J].
CLANCY, RM ;
LESZCZYNSKAPIZIAK, J ;
ABRAMSON, SB .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (03) :1116-1121
[7]   Nitric oxide is a potential down-regulating molecule in autoimmune disease: inhibition of nitric oxide production renders PVG rats highly susceptible to EAE [J].
Cowden, WB ;
Cullen, FA ;
Staykova, MA ;
Willenborg, DO .
JOURNAL OF NEUROIMMUNOLOGY, 1998, 88 (1-2) :1-8
[8]   Evidence for the production of peroxynitrite in inflammatory CNS demyelination [J].
Cross, AH ;
Manning, PT ;
Stern, MK ;
Misko, TP .
JOURNAL OF NEUROIMMUNOLOGY, 1997, 80 (1-2) :121-130
[9]   AMINOGUANIDINE, AN INHIBITOR OF INDUCIBLE NITRIC-OXIDE SYNTHASE, AMELIORATES EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS IN SJL MICE [J].
CROSS, AH ;
MISKO, TP ;
LIN, RF ;
HICKEY, WF ;
TROTTER, JL ;
TILTON, RG .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 93 (06) :2684-2690
[10]  
Ding MZ, 1998, J IMMUNOL, V160, P2560