Limitation of nitric oxide production: cells from lymph node and spleen exhibit distinct difference in nitric oxide production.
Many types of cells in the immune system have been found to produce nitric oxide (NO), which performs multiplex functions. However, in myelin basic protein peptide 68-86 (MBP 68-86)-induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats, we found that elevated NO production was generated from spleen cells (SC), not from lymph node cells (LNC). LNC expressed lower NO synthase 2 (NOS2) and produced lower levels of NO than SC upon MBP 68-86 stimulation. Expression of B7-1(CD80) and B7-2(CD86) molecules was much lower on LNC than on SC. Blocking of B7-1 or B7-2 ligation resulted in reduced NO production by SC. Unlike SC, LNC were resistant to interferon-gamma- or lipopolysaccharide-induced NO production. NO derived from SC suppressed cell proliferation and induced apoptosis in vitro. Addition of N(omega)-nitrol-L-arginine methylester (L-NAME) into cell cultures promoted cell expansion and reduced apoptosis. These results indicate that NO production originates from SC, but not from LNC. Low expression of co-stimulatory molecules and NOS2 of LNC limits NO induction. The high levels of NO derived from SC are involved in the self-limiting mechanisms of autoimmune responses by inhibiting cell expansion and promoting cell apoptosis.
Xu
L
L
Division of Neurology, Unit of Experimental Neurology and Neuroimmunology, Karolinska Institute, Huddinge University Hospital, S 141-86 Huddinge, Stockholm, Sweden.
Yang
J
J
Huang
Y
Y
van der Meide
P H
PH
Levi
M
M
Wahren
B
B
Link
H
H
Xiao
B
B
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000378:metabolism; D017209:Apoptosis; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000378:metabolism; D051940:B7-2 Antigen; D002455:Cell Division; D002478:Cells, Cultured; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000378:metabolism*; D006168:Guinea Pigs; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008198:Lymph Nodes / Q000166:cytology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism; D008969:Molecular Sequence Data; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology*
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497966:Cd86 protein, rat; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D009569:Nitric Oxide; D007371:Interferon-gamma