Immune effector mechanisms of the nitric oxide pathway in malaria: Cytotoxicity versus cytoprotection

Brazilian Journal of Infectious Diseases

Volumn 10, Issue 4, 2006, Pages 283-292

  Nahrevanian, Hossein ^a  

^a PASTEUR INSTITUTE OF IRAN   (Iran)

Author keywords

iNOS; Malaria; Nitric oxide; NO; RNI

Indexed keywords

3,3 BIS(2 AMINOETHYL) 1 HYDROXY 2 OXOTRIAZENE; AMINOGUANIDINE; BACTERIUM LIPOPOLYSACCHARIDE; CYTOKINE; ENDOTOXIN; GAMMA INTERFERON; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; HEMOGLOBIN; HEMOZOIN; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G1; IMMUNOGLOBULIN G2A; IMMUNOGLOBULIN M; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 1; INTERLEUKIN 10; INTERLEUKIN 4; INTERLEUKIN 6; INTERLEUKIN 8; N(G) METHYLARGININE; NITRIC OXIDE; NITRIC OXIDE DONOR; NITRIC OXIDE SYNTHASE INHIBITOR; REACTIVE NITROGEN SPECIES; TUMOR NECROSIS FACTOR ALPHA;

ANTIMALARIAL ACTIVITY; CELL PROTECTION; CELL TYPE; CYTOTOXICITY; DISEASE SEVERITY; ENZYME SYNTHESIS; GENETIC POLYMORPHISM; HOST PARASITE INTERACTION; HOST RESISTANCE; HUMAN; IMMUNE RESPONSE; IMMUNOGLOBULIN PRODUCTION; INFECTION RESISTANCE; INFLAMMATION; MALARIA; MEDICAL RESEARCH; NONHUMAN; PARASITE IMMUNITY; PATHOPHYSIOLOGY; PLASMODIUM MALARIAE; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; STRAIN DIFFERENCE; T LYMPHOCYTE; TH1 CELL; TH2 CELL;

ANIMALS; HOST-PARASITE INTERACTIONS; HUMANS; MALARIA; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE II; PLASMODIUM;

EID: 33947394854     PISSN: 14138670     EISSN: None     Source Type: Journal    
DOI: 10.1590/S1413-86702006000400014     Document Type: Review

References (118)

1. Wernsdorfer W.H., McGregor S.J. Malaria, principles and practice of malariology. UK Churchill Livingstone Ltd, Vol. 2, 1988.
2. Good M.F., Doolan D.L. Immune effector mechanisms in malaria. Curr Opin Immunol 1999;11:412-9.
3. Wakelin D. Intracellular Protozoa; survival within cells. In: Wakelin D. ed. Immunity to parasites, How animals control parasite infections. London, UK, Edward Arnold, 1988.
4. Taylor-Robinson A.W., Smith E.C. A role for cytokines in potentiation of malaria vaccines through immunological modulation of blood stage infection. Immunol Rev 1999;171:105-23.
5. Taylor-Robinson A.W. Parasite variation provides hope for malaria vaccine design. Trends Microbiol 2001;9:157.
6. Garnham, P.C.C. Rodent species of malaria parasites, P. berghei, P. vinckei and P. chabaudi. In: Garnham, P.C.C. ed. Malaria parasites and other haemosporidia. Blackwell scientific publications, 1966.
7. Hommel M. Immunology of malaria. In: World Health Organisation. ed. WHO, Health co-operation papers, Quaderni di cooperazion sanitaria, 1996.
8. Hermsen C.C., Van de Wiel T, Mommers E., et al. Depletion of CD4+ or CD8+ T-cells prevents Plasmodium berghei induced cerebral malaria in end-stage disease. Parasitol 1997;114:7-12.
9. White N.J. Malaria Pathophysiology. In: Sherman IW. ed. Malaria, Parasite biology, Pathogenesis and Protection. 1st edition, ASM Press, Washington D.C., American Society for Microbiology, 1998.
10. White N.J., Ho M. The pathophysiology of malaria. In: White N.J., Ho M. ed. Advances in parasitology, Vol. 31, Academic Press Limited, 1992.
11. Collier L., Balows A., Sussman M. Parasitology. In: Collier L., Balows A., Sussman M. eds. Toply and Wilson's Microbiology and microbial infection., London, UK, 9th edition. Vol. 5, Toply and Wilson, 1998.
12. Phillips R.S., Brannan L.R., Balmer P., et al. Antigenic variation during malaria infection: the contribution from the murine parasite Plasmodium chabaudi. Parasite Immunol 1997;19:427-34.
13. Taylor-Robinson A.W. Regulation of immunity to malaria: valuable lessons learned from murine models. Parasitol Today 1995;2:324-32.
14. Taylor-Robinson A.W. Counter-regulation of T helper 1 cell proliferation by nitric oxide and interleukin-2. Biochem Biophys Res Commun 1997;233:14-9.
15. Clark LA., Al-Yaman F.M., Cowden W.B., et al. Does malarial tolerance, through nitric oxide, explain the low incidence of autoimmune disease intropical Africa? Lancet 1996;348:1492-4.
16. Roitt I.M., Brostoff J., Male D. Immunology. London, 5th edition Mosby Publication, 1998.
17. Deans J.A., Cohen S. Immunology of malaria. Annu Rev Microbiol 1983;37:25-49.
18. Marsh K. Immunology of human malaria. In: Gilles H.M., Warrell D.A. eds. Bruce-Chwatt's Essential Malariology, London, UK, Edward Arnold. 3rd edition ed., 1993.
19. Bogdan C., Rollinghoff M., Diefenbach A. Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity Curr Opin Inummol 2000;12:64-76.
20. Tsuji M., Miyahira. Y., Nussenzweig R.S., et al. Development of antimalaria immunity in mice lacking IFN-gamma receptor. J Immunol 1995;54:5338-44.
21. Chiwakata C.B., Hemmer C.J., Dietrich M. High levels of inducible nitric oxide synthase mRNA are associated with increased monocyte counts in blood and have a beneficial role in Plasmodium falciparum malaria. Infect Immun 2000;68:394-9.
22. Nahrevanian H., Dascombe M.J. The role of nitric oxide and its up/ downstream molecules in malaria: cytotoxic or preventive? SE Asian JTrop Med Public Health 2003;34(S2): 44-50.
23. Modlin R., Rickinson A. Immunity to Infection. Curr Opin Immunol 2000; 12:387-9.
24. Playfair J.H., Taverne J., Bate C.A., et al. The malaria vaccine: anti-parasite or anti-disease? Immunol Today 1990;11:25-7.
25. Ellis G, Adatia I., Yazdanpanah M., et al. Nitrite and nitrate analyses: a clinical biochemistry perspective. Clin Biochem 1998;31:195-220.
26. Granger D.L., Hibbs J.B. High-output nitric oxide: weapon against infection? Trends Microbiol 1996;4:46-7.
27. Mellouk S., Green S.J., Nacy C.A., et al. IFN-ganuna inhibits development of Plasmodium berghei exoerythrocytic stages in hepatocytes by an L-arginine-dependent effector mechanism. J Immunol 1991;146:3971-6.
28. Sam H., Stevenson M.M. In vivo IL-12 production and IL-12 receptors beta1 and beta2 mRNA expression in the spleen are differentially up-regulated in resistant B6 and susceptible A/J mice during early blood-stage Plasmodium chabaudi AS malaria. J Immunol 1999;162:1582-9.
29. Anstey N.M., Hassanali M.Y., Mwaikambo E.D., et al. Nitric oxide appears protective in Tanzanian children with Malaria: Evidence for increased NO production in subclinical infection and suppressed production in clinical and cerebral malaria. In: Moncada S., Stamler J., Gross S., et al. eds. The biology of nitric oxide, London, UK, Portland Press, 1996.
30. Taylor-Robinson A.W. Nitric oxide can be released as well as scavenged by haemoglobin: relevance to its antimalarial activity. Parasite Immunol 1998;20:49-50.
31. Marzinzig M., Nussler A.K., Stadler J., et al. Improved methods to measure end products of nitric oxide in biological fluids: nitrite, nitrate, and S-nitrosothiols. Nitric Oxide: Biology and Chemistry 1997;1:177-189.
32. Rysz J., Luciak M., Kedziora J., et al. Nitric oxide release in the peripheral blood during hemodialysis. Kidney Int 1997;51:294-300.
33. Allen B.W., Piantadosi C.A., Coury L.A.J. Electrode materials for nitric oxide detection. Nitric oxide 2000;4:75-84.
34. Nahrevanian H., Dascombe M.J. Reactive nitrogen intermediate (RNI) levels inside and outside Plasmodium infected red blood cells in murine malaria. J Trop Med Parasitol 2003;26(1):13-9.
35. Tsutsui N., Kamiyama T. Transforming growth factor beta-induced failure of resistance to infection with blood-stage Plasmodium chabaudi in mice. Infect Immun 1999;67:2306-11.
36. Jones I.W., Thomsen L.L., Knowles R., et al. Nitric oxide synthase activity in malaria-infected mice. Parasite Immunol 1996;18:535-8.
37. Jacobs P., Radzioch D., Stevenson M.M. Nitric oxide expression in the spleen, but not in the liver, correlates with resistance to blood-stage malaria in mice. J Immunol 1995;155:5306-13.
38. Klotz F.W., Scheller L.F., Seguin M.C., et al. Co-localization of inducible-nitric oxide synthase and Plasmodium berghei in hepatocytes from rats immunized with irradiated sporozoites. J Immunol 1995;154:3391-5.
39. + T cells. J Exp Med 1994;180:353-8.
40. Scheller L.F., Green S.J., Azad A.F. Inhibition of nitric oxide interrupts the accumulation of CD8+ T cells surrounding Plasmodium berghei-infected hepatocytes. Infect Immun 1997;65:3882-8.
41. Lyons C.R., Orloff G.J., Cunningham J.M. Molecular cloning and functional expression of an inducible nitric oxide synthase from a murine macrophage cell line. J Biol Chem 1992;267:6370-4.
42. Xie Q.W., Cho H.J., Calaycay J., et al. Cloning and characterization of inducible nitric oxide synthase from mouse macrophages. Science 1992;256:225-8.
43. Lancaster J.R.J. A tutorial on the diffusibility and reactivity of free nitric oxide. Nitric Oxide 1997;1:18-30.
44. Ghigo D., Todde R., Ginsburg H., et al. Erythrocyte stages of Plasmodium falciparum exhibit a high nitric oxide synthase (NOS) activity and release an NOS-inducing soluble factor. J Exp Med 1995;182:677-88.
45. Pawloski J.R., Swaminathan R.V., Stamler J.S. Cell-free and erythrocytic S-nitrosohemoglobin inhibits human platelet aggregation. Circulation. 1998;97:263-267.
46. Rockett K.A., Awburn M.M., Cowden W.B., et al. Killing of Plasmodium falciparum in vitro by nitric oxide derivatives. Infect Immun 1991;59:3280-3.
47. Venturini G., Colasanti M., Salvati L., et al. Nitric oxide inhibits falcipain, the Plasmodium falciparum trophozoite cysteine protease. Biochem Biophys Res Commun 2000;7(267):190-3.
48. Taylor-Robinson A.W., Looker, M. Sensitivity of malaria parasites to nitric oxide at low oxygen tensions. Lancet 1998;30(351):1630.
49. Prada J., Malinowski J., Muller S., et al. Effects of Plasmodium vinckei hemozoin on the production of oxygen radicals and nitrogen oxides in murine macrophages. Am J Trop Med Hyg 1996;54:620-4.
50. Paul A., Bryant C., Lawson M.F., et al. Dissociation of lipopolysaccharide-mediated induction of nitric oxide synthase and inhibition of DNA synthesis in RAW 264.7 macrophages and rat aortic smooth muscle cells. Br J Pharmacol 1997;120:1439-44.
51. Shultz P.J., Archer S.L., Rosenberg M.E. Inducible nitric oxide synthase mRNA and activity in glomerular mesangial cells. Kidney Int 1994;46:683-9.
52. Vyas P., Attur M., Ou G.M., et al. Thin layer chromatography: an effective method to monitor citrulline synthesis by NOS activity. In: Moncada S., Stamler J., Gross S., et al. eds. The biology of nitric oxide, London, Portland Press Ltd., 1996.
53. Xie Q.W., Whisnant R., Nathan C. Promoter of the mouse gene encoding calcium-independent nitric oxide synthase confers inducibility by interferon gamma and bacterial lipopolysaccharide. J Exp Med 1993;177:1779-84.
54. Nussler K., Di Silvio M., Billiar T.R., et al. Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokines and endotoxin. J Exp Med 1992;176:261-4.
55. Clark I.A. Does endotoxin cause both the disease and parasite death in acute malaria and babesiosis? Lancet 1978;2:75-7.
56. G-MMLA or indomethacin. In: Moncada S., Stamler J., Gross S., et al. eds. Biology of nitric oxide, London, UK, Portland Press, 1996.
57. Liu S., Adcock I.M., Old R.W., et al. Lipopolysaccharide treatment in vivo induces widespread tissue expression of inducible nitric oxide synthase mRNA. Biochem Biophys Res Commun 1993;96:1208-13.
58. Kasai K., Hattori Y., Banba N., et al. Induction of nitric oxide synthase in human thyrocytes. In: Moncada S., Stamler J., Gross S., et al. eds. Biology of nitric oxide, London, UK, Portland Press, 1996.
59. Mizutani A., Maki H., Torii Y, et al. Ascorbate-dependent enhancement of nitric oxide formation in activated macrophages. Nitric Oxide 1998;2:235-41.
60. Ogura T., Kurashima Y., Esumi H. Regulation of nitric oxide synthase isoform gene expression in human neuronal cells. In: Moncada S., Stamler J., Gross S., et al. eds. Biology of nitric oxide, London, UK, Portland Press, 1996.
61. Nahrevanian H., Dascombe M.J. Nitric oxide and reactive nitrogen intermediates in lethal and nonlethal strains of murine malaria. Parasite Immunol 2001;23:491-501.
62. Nahrevanian H., Dascombe M.J. Expression of inducible nitric oxide synthase (iNOS) mRNA in target organs of lethal and non-lethal strains of murine malaria, Parasite Immunology 2002;24(9-10):471-8.
63. Favre N., Ryffel B., Rudin W. The development of murine cerebral malaria does not require nitric oxide production. Parasitol 1999;118:135-8.
64. Favre N., Ryffel B., Rudin W. Parasite killing in murine malaria does not require nitric oxide production. Parasitol 1999;118:139-43.
65. Granger D.L., Taintor R.R., Boockvar K.S., et al. Measurement of nitrate and nitrite in biological samples using nitrate reductase and Griess reaction. In: Moncada S., Stamler J., Gross S., et al. eds. Biology of nitric oxide, London, UK, Portland Press, 1996.
66. Mohan K., Stevenson M.M. Acquired immunity to asexual blood stages. In: Sherman I.W. ed. Malaria, Parasite biology, Pathogenesis and Protection, Washington D.C., USA, 1st edition, ASM Press, American Society for Microbiology, 2000.
67. Coleman R.M., Rencricca N.J., Stout J.P., et al. Splenic mediated erythrocyte cytotoxicity in malaria. Immunol 1975;29:49-54.
68. Quinn T.C., Wyler D.J. Resolution of acute malaria (Plasmodium berghei in the rat): reversibility and spleen dependence. Am J Trop Med Hyg 1980;29:1-4.
69. Oster C.N., Koontz L.C., Wyler D.J. Malaria in asplenic mice: effects of splenectomy, congenital asplenia and splenic reconstitution on the course of infection. Am J Trop Med Hyg 1980;29:1138-42.
70. Yoneto T., Yoshimoto T., Wang C.R., et al. Gamma interferon production is critical for protective immunity to infection with blood-stage Plasmodium berghei XAT but neither NO production nor NK cell activation is critical. Infect Immun 1999;67:2349-56.
71. Wyler D.J. Splenic functions in malaria. Lymphology 1983;16:121-7.
72. Dockrell H.M., De Souza J.B., Playfair J.H. The role of the liver in immunity to blood-stage murine malaria. Immunol 1980;41:421-30.
73. Stevenson M.M., Kraal G. Histological changes in the spleen and liver of C57BL/6 and A/J mice during Plasmodium chabaudi AS infection. Exp Mol Pathol 1989;51:80-95.
74. Sayles P.C., Cooley A.J., Wassom D.L. A spleen is not necessary to resolve infections with Plasmodium yoelii. Am J Trop Med Hyg 1991;44:42-8.
75. 2 metabolite production and phagocytosis by splenic macrophages during lethal Plasmodium berghei and self-limiting Plasmodium yoelii infection in mice. Infect Immun 1984;44:743-6.
76. Gross A., Geva S., Frankenburg S. Plasmodium berghei: lymphocyte and macrophage dynamics in the spleen of Balb/c mice in the course of infection and after rechallenge of cured mice. Exp Parasitol 1988;65:50-60.
77. Wyler D.J. The spleen in malaria. Ciba Found Symp 1983;94:98-116.
78. Langhorne J., Gillard S., Simon B., et al. Frequencies of CD4+ T cells reactive with Plasmodium chabaudi chabaudi: distinct response kinetics for cells with Th1 and Th2 characteristics during infection. Int Immunol 1989;1:416-24.
79. Allison A.C., Eugui E.M. The role of cell-mediated immune responses in resistance to malaria, with special reference to oxidant stress. Annu Rev Immunol 1983;1:361-92.
80. Bordmann G., Favre N., Rudin W. Malaria toxins: effects on murine spleen and bone marrow cell proliferation and cytokine production in vitro. Parasitol 1997;115:475-83.
81. Playfair J.H., de Souza J.B. Lymphocyte traffic and lymphocyte destruction in murine malaria. Immunol 1982;46:125-33.
82. Suss G., Eichmann K., Kury E., et al. Roles of CD4- and CD8-bearing T lymphocytes in the immune response to the erythrocytic stages of Plasmodium chabaudi. Infect Immun 1988;56:3081-8.
83. Fell A.H., Smith N.C. Immunity to asexual blood stages of Plasmodium: Is resistance to acute malaria adaptive or innate? Parasitol Today 1998;14:364-9.
84. Langhorne J., Pells S., Eichmann K. Phenotypic characterization of splenic T cells from mice infected with Plasmodium chabaudi chabaudi. Scand J Immunol 1993;38:521-8.
85. Weidanz W.P., Melancon-Kaplan J., Cavacini L.A. Cell-mediated immunity to the asexual blood stages of malarial parasites: animal models. Immunol Lett 1990;25:87-95.
86. Van der Heyde H., Elloso M.M., Roopenian D.C., et al. Expansion of the CD4-, CD8- gamma delta T cell subset in the spleens of mice during non-lethal blood-stage malaria. Eur J Immunol 1993;23:1846-50.
87. Mauel J. Macrophages as host cells and reactive defence cells: Immune reactions to parasites. New York, Gustav Fischer Verlag Stuttgart. Fortscritte der Zoologie, Band 27. Zb1. Bakt. Suppl. 12, 1982.
88. Doherty T.M. T-cell regulation of macrophage function. Curr Opin Immunol 1995;7:400-4.
89. Taylor-Robinson A.W. Immunity to asexual blood stages of Plasmodia: is resistance to acute malaria adaptive or innate? Parasitol Today 1999;15:208.
90. Carter R., Walliker D. New observations on the malaria parasites of rodents of the Central African Republic - Plasmodium vinckei petteri subsp. nov. and Plasmodium chabaudi, Landau, 1965. Ann Trop Med Parasitol 1975;69:187-96.
91. Cox F.E.G. Major animal models in malaria research: rodent. In: Wernsdorfer W.H., McGregor S.J. eds. Malaria: Principles and Practice of Malariology, UK, Churchill Livingstone, 1988.
92. Landau I., Chabaud A.G. Natural infection by 2 plasmodia of the rodent Thamnomys rutilans in the Central African Republic. C R Acad Sci Hebd Seances 1965;261:230-2.
93. Taylor B.S., Kim Y.M., Wang Q., et al. Nitric oxide down-regulates hepatocyte-inducible nitric oxide synthase gene expression. Arch Surg 1997;132:1177-83.
94. Amante F.H., Good M.F. Prolonged Th1-like response generated by a Plasmodium yoelii-specific T cell clone allows complete clearance of infection in reconstituted mice. Parasite Immunol 1997;19:111-26.
95. Hirunpetcharat C., Finkelman F., Clark I.A., Good M.F. Malaria parasite-specific Th1-like T cells simultaneously reduce parasitemia and promote disease. Parasite Immunol 1999;21:319-29.
96. Rockett K.A., Awburn M.M., Rockett E.J., et al. Possible role of nitric oxide in malarial immunosuppression. Parasite Immunol 1994;16:243-9.
97. Stevenson M.M., Tam M.F., Wolf S.F., et al. IL-12-induced protection against blood-stage Plasmodium chabaudi AS requires IFN-gamma and TNF-alpha and occurs via a nitric oxide- dependent mechanism. J Immunol 1995;155:2545-56.
98. Taylor-Robinson A.W. Murine models of cerebral malaria: A qualified defence. Parasitol. Today 1995;11:407-8.
99. Basir R., Dascombe M.J. Nitric oxide involvement in rodent malaria. Asia Pacific J. Pharmacol 2000;14:S72-3.
100. Balmer P., Phillips H.M., Maestre A.E., et al. The effect of nitric oxide on the growth of Plasmodium falciparum, P. chabaudi and P. berghei in vitro. Parasite Immunol 2000;22:97-106.
101. Dascombe M.J., Nahrevanian H. Pharmacological assessment of the role of nitric oxide in mice infected with lethal and nonlethal species of malaria, Parasite Immunol 2003;25(3):149-59.
102. Burdon M.G., Butler A.R., Renton L.M. A study of antibacterial activity of nitric oxide donor compounds. In: Moncada S., Stamler J., Gross S., et al. eds. The biology of nitric oxide, London, Portland Press Ltd., 1996.
103. Helmby H., Troye-Blomberg M. Differential immunoglobulin E and cytokine responses in BALB/c and C57B1/6 mice during repeated infections with blood-stage Plasmodium chabaudi malaria. Parasite Immumol 2000;22:185-90.
104. Taylor-Robinson A.W., Stephen Phillips R., Severn A., et al. The role of TH1 and TH2 cells in a rodent malaria infection. Science 1993;260:1931-4.
105. Favila-Castillo L., Monroy-Ostria A., Garcia-Tapia D. Plasmodium chabaudi chabaudi: effect of low parasitemias on immunity in CB6F1 mice. Exp Parasitol 1999;92:73-80.
106. Jakobsen P.H., Bate C.A., Taverne J., et al. Malaria: toxins, cytokines and disease. Parasite Immunol. 1995;17:223-31.
107. Yoshimoto T., Takahama Y., Wang C.R., et al. A pathogenic role of IL-12 in blood-stage murine malaria lethal strain Plasmodium berghei NK65 infection. J Immunol 1998;160:5500-5.
108. Jacobs P., Radzioch D., Stevenson M.M. In vivo regulation of nitric oxide production by tumor necrosis factor alpha and gamma interferon, but not by interleukin-4, during blood stage malaria in mice. Infect Immun 1996;64:44-9.
109. Abbas A.K., Lichtman A.H., Pober J.S. Effector mechanisms of immune responses. In: Abbas A.K., Lichtman A.H., Pober J.S. eds. Cellular and Molecular Immunology, USA, W.B. Saunders Company, 3rd edition, 1997.
110. Geller D.A., Nussler A.K., Di Silvio M., et al. Cytokines, endotoxin, and glucocorticoids regulate the expression of inducible nitric oxide synthase in hepatocytes. Proc Natl Acad Sci 1993;90:522-6.
111. Grau G., Piguet P.F., Pointaire P. Cytokines and Malaria; Duality of effects in pathology and protection. In: Kunkel S.L., Remick D.G eds. Cytokines in health and disease, USA, New York, Marcel Dekker, Inc., 1992.
112. Bogdan C., Rollinghoff M., Diefenbach A. The role of nitric oxide in innate immunity. Immunol Rev 2000;173:17-26.
113. Stefano G.B., Magazine H.I. Nitric oxide autoregulation and its significance. Modern Aspects Immunobiol 2001;1:182-6.
114. Mosmann T.R., Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 1996;17:138-46.
115. Liew F.Y. Regulation of nitric oxide synthase in macrophages. In: Moncada S., Stamler J., Gross S., et al. eds. The biology of nitric oxide: 2 Enzymology, Biochemistry and Immunology, London, UK, Portland Press, 1992.
116. Levesque M.C., Hobbs M.R., Anstey N.M., et al. Nitric oxide synthase type 2 promoter polymorphisms, nitric oxide production, and disease severity in Tanzanian children with malaria. J Infect Dis 1999;180:1994-2002.
117. Brown G.V., Beck H., Molyneux M., et al. Molecular approaches to epidemiology and clinical aspects of malaria. Parasitol Today 2000;16:448-51.
118. Kun J.F., Mordmuller B., Lell B., et al. Polymorphism in promoter region of inducible nitric oxide synthase gene and protection against malaria. Lancet 1998;351:265-6.