Potential role of immune system activation-associated production of neopterin derivatives in humans

Inflammation Research

Volumn 52, Issue 8, 2003, Pages 313-321

  Hoffmann, G ^a   Wirleitner, B ^b   Fuchs, D ^b,c  

^a UNIVERSITY OF BONN   (Germany)

^b UNIVERSITY OF INNSBRUCK   (Austria)

^c LUDWIG BOLTZMANN INSTITUTE FOR LUNG VASCULAR RESEARCH   (Austria)

Author keywords

Immune activation; Interferon gamma; Macrophages; Nitric oxide; Pteridines

Indexed keywords

GAMMA INTERFERON; INTERFERON; NEOPTERIN; NEOPTERIN DERIVATIVE; NITRIC OXIDE; REACTIVE OXYGEN METABOLITE; UNCLASSIFIED DRUG;

BLOOD LEVEL; CELL METABOLISM; CELL SECRETION; CELLULAR IMMUNITY; CYTOKINE RELEASE; CYTOTOXICITY; DENDRITIC CELL; HUMAN; IMMUNOSTIMULATION; INFLAMMATION; MACROPHAGE; REVIEW; URINE LEVEL;

CELL LINE; HUMANS; IMMUNE SYSTEM; MODELS, BIOLOGICAL; MOLECULAR STRUCTURE; NEOPTERIN; OXIDATIVE STRESS;

EID: 0042162960     PISSN: 10233830     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00011-003-1181-9     Document Type: Review

References (111)

1. Sakurai A, Goto M. Neopterin: Isolation from human urine. J Biochem (Tokyo) 1967; 61: 142-5.
2. Wachter H, Hausen A, Grassmayr K. Increased urinary excretion of neopterin in patients with malignant tumors and with virus diseases. Hoppe Seylers Z Physiol Chem 1979; 360: 1957-60.
3. Fuchs D, Hausen A, Huber C, Margreiter R, Reibnegger G, Spielberger M et al. Pteridine secretion as a marker for the proliferation of alloantigen-induced lymphocytes. Hoppe Seylers Z Physiol Chem 1982; 363: 661-4.
4. Huber C, Fuchs D, Hausen A, Margreiter R, Reibnegger G, Spielberger M et al. Pteridines as a new marker to detect human T cells activated by allogeneic or modified self major histocompatibility complex (MHC) determinants. J Immunol 1983; 130: 1047-50.
5. Margreiter R, Fuchs D, Hausen A, Huber C, Reibnegger G, Spielberger M et al. Neopterin as a new biochemical marker for diagnosis of allograft rejection. Experience based upon evaluation of 100 consecutive cases. Transplantation 1983; 36: 650-3.
6. Reynolds JJ, Brown GM. The biosynthesis of folic acid. J Biol Chem 1967; 239: 317-25.
7. Werner-Felmayer G, Werner ER, Fuchs D, Hausen A, Reibnegger G, Wachter H. Neopterin formation and tryptophan degradation by a human myelomonocytic cell line (THP-1) upon cytokine treatment. Cancer Res 1990; 50: 2863-7.
8. Werner ER, Werner-Felmayer G, Fuchs D, Hausen A, Reibnegger G, Yim JJ et al. Tetrahydrobiopterin biosynthetic activities in human macrophages, fibroblasts, THP-1, and T 24 cells. GTP-cyclohydrolase I is stimulated by interferon-gamma, and 6-pyruvoyl tetrahydropterin synthase and sepiapterin reductase are constitutively present. J Biol Chem 1990; 265: 3189-92.
9. Werner ER, Werner-Felmayer G, Fuchs D, Hausen A, Reibnegger G, Wels G et al. 6-Pyruvoyl tetrahydropterin synthase assay in extracts of cultured human cells using high-performance liquid chromatography with fluorescence detection of biopterin. J Chromatogr 1991; 570: 43-50.
10. Weiss G, Glaser K, Kronberger P, Ambach E, Fuchs D, Bodner E et al. Distinct distributions of D-erythro-neopterin in arteries and veins and its recovery by an enterohepatic circulation. Biol Chem Hoppe Seyler 1992; 373: 289-94.
11. Fuchs D, Stahl-Hennig C, Gruber A, Murr C, Hunsmann G, Wachter H. Neopterin - its clinical use in urinalysis. Kidney Int Suppl 1994; 47: S8-11.
12. Huber C, Batchelor JR, Fuchs D, Hausen A, Lang A, Niederwieser D et al. Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon- gamma. J Exp Med 1984; 160: 310-6.
13. Wirleitner B, Reider D, Ebner S, Bock G, Widner B, Jaeger M et al. Monocyte-derived dendritic cells release neopterin. J Leukoc Biol 2002; 72: 1148-53.
14. Werner-Felmayer G, Baier-Bitterlich G, Fuchs D, Hausen A, Murr C, Reibnegger G et al. Detection of bacterial pyrogens on the basis of their effects on gamma interferon-mediated formation of neopterin or nitrite in cultured monocyte cell lines. Clin Diagn Lab Immunol 1995; 2: 307-13.
15. Andert SE, Griesmacher A, Zuckermann A, Muller MM. Neopterin release from human endothelial cells is triggered by interferon-gamma. Clin Exp Immunol. 1992; 88: 555-8.
16. Moutabarrik A, Takahara S, Nakanishi I, Kokado Y, Takano Y, Kameoka H et al. Interferon-gamma stimulates neopterin release from cultured kidney epithelial cells. Scand J Immunol 1994; 39: 27-30.
17. Walter R, Linscheid P, Blau N, Kierat L, Schaffner A, Schoedon G. Induction of tetrahydrobiopterin synthesis in human umbilical vein smooth muscle cells by inflammatory stimuli. Immunol Lett 1998; 60: 13-7.
18. Werner-Felmayer G., Werner ER, Fuchs D, Hausen A, Reibnegger G, Schmidt K et al. Pteridine biosynthesis in human endothelial cells. Impact on nitric oxide-mediated formation of cyclic GMP. J Biol Chem 1993; 268: 1842-6.
19. Wachter H, Fuchs D, Hausen A, Reibnegger G, Werner ER. Neopterin as marker for activation of cellular immunity: immunologic basis and clinical application. Adv Clin Chem 1989; 27: 81-141.
20. Fredrikson S, Link H, Eneroth P. CSF neopterin as marker of disease activity in multiple sclerosis. Acta Neurol Scand 1987; 75: 352-5.
21. Krause A, Protz H, Goebel KM. Correlation between synovial neopterin and inflammatory activity in rheumatoid arthritis. Ann Rheum Dis 1989; 48: 636-40.
22. Reibnegger G, Fuchs D, Zangerle R, Wachter H. Increased neopterin concentration in saliva of patients with HIV-1 infection. Clin Chem 1990; 36: 1379-80.
23. Hagberg L, Dotevall L, Norkrans G, Larsson M, Wachter H, Fuchs D. Cerebrospinal fluid neopterin concentrations in central nervous system infection. J Infect Dis 1993; 168: 1285-8.
24. Daito K, Suou T, Kawasaki H. Serum and urinary neopterin levels in patients with chronic active hepatitis B treated with interferon. Res Commun Chem Pathol Pharmacol 1994; 83: 303-16.
25. Fuchs D, Hausen A, Kofler M, Kosanowski H, Reibnegger G, Wachter H. Neopterin as an index of immune response in patients with tuberculosis. Lung 1984; 162: 337-46.
26. Strohmaier W, Redl H, Schlag G, Inthorn D. D-erythro-neopterin plasma levels in intensive care patients with and without septic complications. Crit Care Med 1987; 15: 757-60.
27. Fuchs D, Spira TJ, Hausen A, Reibnegger G, Werner ER, Felmayer GW et al. Neopterin as a predictive marker for disease progression in human immunodeficiency virus type 1 infection. Clin Chem 1989; 35: 1746-9.
28. Fahey JL, Taylor JM, Detels R, Hofmann B, Melmed R, Neshanian P et al. The prognostic value of cellular and serologic markers in infection with human immunodeficiency virus type 1. N Engl J Med 1990; 322: 166-72.
29. Reibnegger G, Egg D, Fuchs D, Gunther R, Hausen, A, Werner ER et al. Urinary neopterin reflects clinical activity in patients with rheumatoid arthritis. Arthritis Rheum 1986; 29: 1063-70.
30. Manna R, Salvatore M, Di Leo MA, Scuderi F, Greco AV, Ghirlanda G et al. Relationship between urinary neopterin excretion and islet cell antibodies in type 1 (insulin-dependent) diabetes. Diabetes Res 1991; 17: 33-6.
31. Leohirun L, Thuvasethakul P, Sumethkul V, Pholcharoen T, Boonpucknavig V. Urinary neopterin in patients with systemic lupus erythematosus. Clin Chem 1991; 37: 47-50.
32. Davies SV, Carter C, Williams MD, Pollock A, Leeming RJ. The significance of neopterin and biopterin concentrations at presentation in haematological malignancies. Clin Lab Haematol 1992; 14: 41-6.
33. Fuchs D, Granditsch G, Hausen A, Reibnegger G, Wachter H. Urinary neopterin excretion in coeliac disease. Lancet 1983; 2: 463-4.
34. Samsonov M, Nassonov E, Dhzuzenova B, Belenkov Y, Nassonova V, Wachter H et al. Serum neopterin in acute rheumatic fever. Clin Chem 1993; 39: 693-5.
35. Frick J, Aulitzky W, Fuchs D, Hausen A, Joos H, Reibnegger G et al. The value of urinary neopterin as an immunological parameter in patients with malignant tumors of the genitourinary tract. Urol Int 1985; 40: 155-9.
36. Hausen A, Bichler A, Fuchs D, Hetzel H, Reibnegger G, Wachter H. Neopterin, a biochemical indicator of cellular immune reactions, in the detection and control of patients with neoplastic diseases. Cancer Detect Prev 1985; 8: 121-8.
37. Reibnegger G, Fuchs D, Fuith LC, Hausen A, Werner ER, Werner-Felmayer G et al. Neopterin as a marker for activated cell-mediated immunity: Application in malignant disease. Cancer Detect Prevent 1991; 15: 483-90.
38. Niederwieser D, Huber C, Gratwohl A, Bannert P, Fuchs D, Hausen A et al. Neopterin as a new biochemical marker in the clinical monitoring of bone marrow transplant recipients. Transplantation 1984; 38: 497-500.
39. Wolf J, Musch E, Neuss H, Klehr U. Neopterin in the serum and urine in the differential diagnosis of disorders of kidney function following kidney transplantation. Klin Wochenschr 1987; 65: 225-31.
40. Honlinger M, Fuchs D, Hausen A, Reibnegger G, Schonitzer D, Werner ER et al. Serum neopterin determination for the additional safeguarding of blood transfusions. Our experiences with 76,587 blood donors. Dtsch Med Wochenschr 1989; 114: 172-6.
41. Peters KM, Bruchhausen B, Leusch HG, Forst R. The selection of spongiosa donors for a bone bank. Dtsch Med Wochenschr 1991; 116: 1897-1902.
42. Schratt HE, Regel G, Lobenhoffer P, Tscherne H. Organization of a bone and tissue bank. Consequences for organization of bone and tissue banks after HIV and hepatitis C infections. Unfallchirurg 1996; 99: 880-8.
43. Nathan CF. Peroxide and pteridine: a hypothesis on the regulation of macrophage antimicrobial activity by interferon gamma. Interferon 1986; 7: 125-43.
44. Woll E, Weiss G, Fuchs D, Lang F, Wachter H. Effect of pteridine derivatives on intracellular calcium concentration in human monocytic cells. FEBS Lett 1993; 318: 249-52.
45. Kojima S, Icho T, Mori H, Arai T. Enhancing potency of neopterin toward B-16 melanoma cell damage induced by UV-A irradiation and its possible application for skin tumor treatment. Anticancer Res 1995; 15: 1975-80.
46. Murr C, Fuchs D, Gossler W, Hausen A, Reibnegger G, Werner ER et al. Enhancement of hydrogen peroxide-induced luminol-dependent chemiluminescence by neopterin depends on the presence of iron chelator complexes. FEBS Lett 1994; 338: 223-6.
47. Wede I, Widner B, Fuchs D. Neopterin derivatives modulate toxicity of reactive species on Escherichia coli. Free Rad Res 1999; 31: 381-8.
48. Weiss G, Fuchs D, Hausen A, Reibnegger G, Werner ER, Werner-Felmayer G et al. Neopterin modulates toxicity mediated by reactive oxygen and chloride species. FEBS Lett 1993; 321: 89-92.
49. 2-induced luminol chemiluminescence: mechanistic aspects. Free Radic Biol Med 1996; 21: 449-56.
50. Widner B, Baier-Bitterlich G, Wede I, Wirleitner B, Fuchs D. Neopterin derivatives modulate the nitration of tyrosine by peroxynitrite. Biochem Biophys Res Commun 1998; 248: 341-6.
51. Schobersberger W, Hoffmann G, Grote J, Wachter H, Fuchs D. Induction of inducible nitric oxide synthase expression by neopterin in vascular smooth muscle cells. FEBS Lett 1995; 377: 461-4.
52. Kilbourn RG, Traber DL, Szabo C. Nitric oxide and shock. Dis Mon 1997; 43: 277-348.
53. Strohmaier W, Werner ER, Wachter H, Redl H, Schlag G. Pteridine and nitrite/nitrate formation in experimental septic and traumatic shock. Shock 1996; 6: 254-8.
54. Adamik B, Golebiowska B, Kubler-Kielb J, Gamian A, Kubler A. Neopterin and nitric oxide metabolites during sepsis in critically ill patients. Int Care Med 1999; 25: S150.
55. Hoffmann G, Schobersberger W, Frede S, Pelzer L, Fandrey J, Wachter H et al. Neopterin activates transcription factor nuclear factor-kappa B in vascular smooth muscle cells. FEBS Lett 1996; 391: 181-4.
56. Schreck R, Meier B, Mannel DN, Droge W, Baeuerle PA. Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells. J Exp Med 1992; 175: 1181-94.
57. Barak M, Gruener N. Neopterin augmentation of tumor necrosis factor production. Immunol Lett 1991; 30: 101-6.
58. Hoffmann G, Frede S, Kenn S, Smolny M, Wachter H, Fuchs D et al. Neopterin-induced tumor necrosis factor-alpha synthesis in vascular smooth muscle cells in vitro. Int Arch Allergy Immunol 1998; 116: 240-5.
59. Beutler B, Grau GE. Tumor necrosis factor in the pathogenesis of infectious diseases. Crit Care Med 1993; 21: S423-35.
60. Offner F, Philippe J, Vogelaers D, Colardyn F, Baele G, Baudrihaye M et al. Serum tumor necrosis factor levels in patients with infectious disease and septic shock. J Lab Clin Med 1990; 116: 100-5.
61. Margreiter J, Schlager A, Balogh A, Maier H, Balogh D, Lindner KH et al. Exogenous neopterin causes cardiac contractile dysfunction in the isolated perfused rat heart. J Mol Cell Cardiol 2000; 32: 1265-74.
62. Rieder J, Amann A, Schloesser M, Czechowski M, Seibel M, Marth C et al. Suppressive effects of neopterin on inducible nitric oxide synthase gene expression in ovarian carcinoma cells in vitro. Pteridines 2001; 12: 140-6.
63. Reibnegger G, Hetzel H, Fuchs D, Fuith LC, Hausen A, Werner ER et al. Clinical significance of neopterin for prognosis and follow-up in ovarian cancer. Cancer Res 1987; 47: 4977-81.
64. Rieder J, Marth C, Totzke G, Smolny M, Seibel M, Hoffmann G. Different patterns of inducible nitric oxide synthase gene expression in ovarian carcinoma cell lines. Anticancer Res 2000; 20: 3251-8.
65. Rieder J, Jahnke R, Schloesser M, Seibel M, Czechowski M, Marth C et al. Nitric oxide-dependent apoptosis in ovarian carcinoma cell lines. Gynecol Oncol 2001; 82: 172-6.
66. Marth C, Weger A, Muller-Holzner E, Zeimet AG, Moncayo-Naveda H, Daxenbichler G et al. The prognostic value of nuclear roundness and neopterin in ovarian cancer. Eur J Cancer 1993; 29A: 1863-8.
67. Hoffmann G, Kenn S, Wirleitner B, Deetjen C, Frede S, Smolny M et al. Neopterin induces nitric oxide-dependent apoptosis in rat vascular smooth muscle cells. Immunobiology 1998; 199: 63-73.
68. Schobersberger W, Hoffmann G, Hobisch HP, Bock G, Volkl H, Baier-Bitterlich G et al.. Neopterin and 7,8-dihydroneopterin induce apoptosis in the rat alveolar epithelial cell line L2. FEBS Lett 1996; 397: 263-8.
69. Baier-Bitterlich G, Fuchs D, Murr C, Reibnegger G, Werner-Felmayer G, Sgonc R et al. Effect of neopterin and 7,8-dihydroneopterin on tumor necrosis factor-alpha induced programmed cell death. FEBS Lett 1995; 364: 234-8.
70. Weiss G, Willeit J, Kiechl S, Fuchs D, Jarosch E, Oberhollenzer F et al. Increased concentrations of neopterin in carotid atherosclerosis. Atherosclerosis 1994; 106: 263-71.
71. Buttery LD, Springall DR, Chester AH, Evans TJ, Standfield EN, Parums DV et al. Inducible nitric oxide synthase is present within human atherosclerotic lesions and promotes the formation and activity of peroxynitrite. Lab Invest 1996; 75: 77-85.
72. Herpfer I, Greilberger J, Ledisnki G, Widner B, Fuchs D, Jurgens G. Neopterin and 7,8-dihydroneopterin interfere with low density lipoprotein oxidation mediated by peroxynitrite and/or copper. Free Radic Res 2002; 36: 509-20.
73. Kiechl S, Lorenz E, Reindl M, Wiedermann CJ, Oberhollenzer F, Bonora E et al. Toll-like receptor 4 polymorphisms and atherogenesis. N Engl J Med 2002; 347: 185-92.
74. Schennach H, Murr C, Gachter E, Mayersbach P, Schonitzer D, Fuchs D. Association between neopterin production and other parameters in a population of blood donors. Pteridines (in press).
75. Compton CN, Franko AP, Murray MT, Diebel LN, Dulchavsky SA. Signaling of apoptotic lung injury by lipid hydroperoxides. J Trauma 1998; 44: 783-8.
76. Hoffmann G, Rieder J, Smolny M, Seibel M, Wirleitner B, Fuchs D et al. Neopterin-induced expression of intercellular adhesion molecule-1 (ICAM- 1) in type II-like alveolar epithelial cells. Clin Exp Immunol 1999; 118: 435-40.
77. Prior C, Frank A, Fuchs D, Hausen A, Judmaier G, Reibnegger G et al. Urinary neopterin excretion in pulmonary sarcoidosis: correlation to clinical course of the disease. Clin Chim Acta 1988; 177: 211-20.
78. Saito M, Chihara J, Mouri T, Kurachi D, Yamamoto T and Nakajima S. Elevated local production of neopterin from alveolar macrophages in patients with internal lung diseases. Gen Pharmacol 1996; 27: 483-6.
79. Waydhas C, Nast-Kolb D, Jochum M, Trupka A, Lenk S, Fritz H et al. Inflammatory mediators, infection, sepsis, and multiple organ failure after severe trauma. Arch Surg 1992; 127: 460-7.
80. Baumer I, Zissel G, Schlaak M, Muller-Quernheim J. Shed soluble ICAM-1 molecules in bronchoalveolar lavage cell supernatants and serum of patients with pulmonary sarcoidosis. Lung 1997; 175: 105-16.
81. Diez-Ruiz A, Kaiser G, Jager H, Birkmann J, Tilz GP, Wachter H et al. Increased levels of serum intercellular adhesion molecule 1 in HIV infection are related to immune activation. Int Arch Allergy Immunol 1993; 102: 56-60.
82. Luna-Casado L, Diez-Ruiz A, Gutierrez-Gea F, Santos-Perez JL, Rico-Irles J, Wachter H et al. Increased peripheral mononuclear cells expression of adhesion molecules in alcoholic cirrhosis: its relation to immune activation. J Hepatol 1997; 27: 477-83.
83. Dhondt JL, Darras A, Mulliez P, Hayte JM, Crinquette J. Unconjugated pteridines in bronchoalveolar lavage as indicators of alveolar macrophage activation. Chest 1989; 95: 348-51.
84. Kojima S, Nomura T, Icho T, Kajiwara Y, Kitabatake K, Kubota K. Inhibitory effect of neopterin on NADPH-dependent superoxide- generating oxidase of rat peritoneal macrophages. FEBS Lett 1993; 329: 125-8.
85. Oettl K, Dikalov S, Freisleben HJ, Mlekusch W, Reibnegger G. Spin trapping study of antioxidant properties of neopterin and 7,8-dihydroneopterin. Biochem Biophys Res Commun 1997; 234: 774-8.
86. Kuppusamy P, Zweier JL. Characterization of free radical generation by xanthine oxidase. Evidence for hydroxyl radical generation. J Biol Chem 1989; 264: 9880-4.
87. Oettl K, Reibnegger G. Pteridines as inhibitors of xanthine oxidase: structural requirements. Biochim Biophys Acta 1999; 1430: 387-95.
88. Wede I, Altindag ZZ, Widner B, Wachter H, Fuchs D. Inhibition of xanthine oxidase by pterins. Free Radic Res 1998; 29: 331-8.
89. Haberland A, Schutz AK, Schimke I. The influence of lipid peroxidation products (malondialdehyde, 4-hydroxynonenal) on xanthine oxidoreductase prepared from rat liver. Biochem Pharmacol 1992; 43: 2117-20.
90. Arai T, Endo N, Yamashita K, Sasada M, Mori H, Ishii H et al. 6-Formylpterin, a xanthine oxidase inhibitor, intracellularly generates reactive oxygen species involved in apoptosis and cell proliferation. Free Rad Biol Med 2001; 30: 248-59.
91. Heales SJ, Blair JA, Meinschad C, Ziegler I. Inhibition of monocyte luminol-dependent chemiluminescence by tetrahydrobiopterin, and the free radical oxidation of tetrahydrobiopterin, dihydrobiopterin and dihydroneopterin. Cell Biochem Funct 1988; 6: 191-5.
92. Gieseg SP, Reibnegger G, Wachter H, Esterbauer H. 7,8-Dihydroneopterin inhibits low density lipoprotein oxidation in vitro. Evidence that this macrophage secreted pteridine is an anti-oxidant. Free Radic Res 1995; 23: 123-36.
93. Gieseg SP, Whybrow J, Glubb D, Rait C. Protection of U937 cells from free radical damage by the macrophage synthesized antioxidant 7,8-dihydroneopterin. Free Radic Res 2001; 35: 311-8.
94. Gieseg SP, Maghzai G, Glubb D. Protection of erythrocytes by the macrophage synthesized antioxidant 7,8-dihydroneopterin. Free Radic Res 2001; 34: 123-36.
95. Oettl K, Wirleitner B, Baier-Bitterlich G, Grammer T, Fuchs D, Reibnegger G. Formation of oxygen radicals in solutions of 7,8-dihydroneopterin. Biochem Biophys Res Commun 1999; 264: 262-7.
96. Oettl K, Pfleiderer W, Reibnegger G. Formation of oxygen radicals in solutions of different 7,8-dihydropterins: quantitative structure-activity relationships. Helv Chim Acta 2000; 5: 954-65.
97. Oettl K, Reibnegger G. Pteridine derivatives as modulators of oxidative stress. Curr Drug Metab 2002; 3: 203-9.
98. Horejsi R, Jung C, Moller R, Tafeit E, Reibnegger G. Generation of carbon monoxide and iron from hemeproteins in the presence of 7,8-dihydroneopterin. Biochim Biophys Acta 2002; 1571: 124-30.
99. Baier-Bitterlich G, Baier G, Fuchs D, Bock G, Hausen A, Utermann G et al. Role of 7,8-dihydroneopterin in T-cell apoptosis and HTLV-1 transcription in vitro. Oncogene 1996; 13: 2281-5.
100. Baier-Bitterlich G, Fuchs D, Wachter H. 7,8-Dihydroneopterin upregulates interferon-gamma promoter in T cells. Immunobiology 1996; 196: 350-5.
101. Wirleitner B, Baier-Bitterlich G, Bock G, Widner B, Fuchs D. 7,8-Dihydroneopterin-induced apoptosis in Jurkat T lymphocytes: a comparison with anti-Fas- and hydrogen peroxide-mediated cell death. Biochem Pharmacol 1998; 56: 1181-7.
102. Wirleitner B, Czaputa R, Oettl K, Bock G, Widner B, Reibnegger G et al. Induction of apoptosis by 7,8-dihydroneopterin, involvement of radical formation. Immunobiology 2001; 203: 629-41.
103. Enzinger C, Wirleitner B, Spoettl N, Bock G, Fuchs D, Baier-Bitterlich G. Reduced pteridine derivatices induce apoptotsis in PC 12 cells. Neruochem Int 2002; 41: 71-8.
104. Speth C, Stoeckl G, Fuchs D, Wirleitner B, Widner B, Wuerzner R et al. Inflammation marker 7,8-dihydroneopterin induces apoptosis of neurons and glial cells: a potential contribution to neurodegenerative processes. Immunobiology 2000; 202: 460-76.
105. Spoettl N, Wirleitner B, Boeck G, Widner B, Fuchs D, Baier-Bitterlich G. Reduced pteridine derivatives induce apoptosis in human neuronal NT2/HNT cells. Immunobiology 2000; 201: 478-91.
106. Brew BJ, Bhalla RB, Paul M, Gallardo H, McArthur JC, Schwartz MK et al. Cerebrospinal fluid neopterin in human immunodeficiency virus type 1 infection. Ann Neurol 1990; 28: 556-60.
107. Griffin DE, McArthur JC, Cornblath DR. Neopterin and interferon-gamma in serum and cerebrospinal fluid of patients with HIV-associated neurologic disease. Neurology 1991; 41: 69-74.
108. Fukushima T, Nixon JC. Analysis of reduced forms of biopterin in biological tissues and fluids. Anal Biochem 1980; 102: 176-88.
109. Widner B, Mayr C, Wirleitner B, Fuchs D. Oxidation of 7,8-dihydroneopterin by hypochlorous acid yields neopterin. Biochem Biocphys Res Commun 2000; 275: 301-11.
110. Cammer W. Apoptosis of oligodendrocytes in secondary cultures from neonatal rat brains. Neurosci Lett 2002; 327: 123-7.
111. Fallarino F, Grohmann U, Vacca C, Bianchi R, Orabona C, Fioretti MC et al. T cell apoptosis by tryptophan catabolism. Cell Death Diff 2002; 9: 1069-77.