Abstract
We have investigated the in vitro susceptibility of the human malaria parasite Plasmodium falciparum to killing by nitric oxide and related molecules. A saturated solution of nitric oxide did not inhibit parasite growth, but two oxidation products of nitric oxide (nitrite and nitrate ions) were toxic to the parasite in millimolar concentrations. Nitrosothiol derivatives of cysteine and glutathione were found to be about a thousand times more active (50% growth inhibitory concentration, approximately 40 microM) than nitrite.
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- Adams L. B., Hibbs J. B., Jr, Taintor R. R., Krahenbuhl J. L. Microbiostatic effect of murine-activated macrophages for Toxoplasma gondii. Role for synthesis of inorganic nitrogen oxides from L-arginine. J Immunol. 1990 Apr 1;144(7):2725–2729. [PubMed] [Google Scholar]
- Beckman J. S., Beckman T. W., Chen J., Marshall P. A., Freeman B. A. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1620–1624. doi: 10.1073/pnas.87.4.1620. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bredt D. S., Hwang P. M., Snyder S. H. Localization of nitric oxide synthase indicating a neural role for nitric oxide. Nature. 1990 Oct 25;347(6295):768–770. doi: 10.1038/347768a0. [DOI] [PubMed] [Google Scholar]
- Butcher G. A., Garland T., Ajdukiewicz A. B., Clark I. A. Serum tumor necrosis factor associated with malaria in patients in the Solomon Islands. Trans R Soc Trop Med Hyg. 1990 Sep-Oct;84(5):658–661. doi: 10.1016/0035-9203(90)90134-z. [DOI] [PubMed] [Google Scholar]
- Cavacini L. A., Guidotti M., Parke L. A., Melancon-Kaplan J., Weidanz W. P. Reassessment of the role of splenic leukocyte oxidative activity and macrophage activation in expression of immunity to malaria. Infect Immun. 1989 Dec;57(12):3677–3682. doi: 10.1128/iai.57.12.3677-3682.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clark I. A., Hunt N. H., Butcher G. A., Cowden W. B. Inhibition of murine malaria (Plasmodium chabaudi) in vivo by recombinant interferon-gamma or tumor necrosis factor, and its enhancement by butylated hydroxyanisole. J Immunol. 1987 Nov 15;139(10):3493–3496. [PubMed] [Google Scholar]
- Clark I. A., Hunt N. H. Evidence for reactive oxygen intermediates causing hemolysis and parasite death in malaria. Infect Immun. 1983 Jan;39(1):1–6. doi: 10.1128/iai.39.1.1-6.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Collier J., Vallance P. Second messenger role for NO widens to nervous and immune systems. Trends Pharmacol Sci. 1989 Nov;10(11):427–431. doi: 10.1016/s0165-6147(89)80001-x. [DOI] [PubMed] [Google Scholar]
- Ding A. H., Nathan C. F., Stuehr D. J. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol. 1988 Oct 1;141(7):2407–2412. [PubMed] [Google Scholar]
- Dockrell H. M., Playfair J. H. Killing of blood-stage murine malaria parasites by hydrogen peroxide. Infect Immun. 1983 Jan;39(1):456–459. doi: 10.1128/iai.39.1.456-459.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
- Granger D. L., Hibbs J. B., Jr, Perfect J. R., Durack D. T. Metabolic fate of L-arginine in relation to microbiostatic capability of murine macrophages. J Clin Invest. 1990 Jan;85(1):264–273. doi: 10.1172/JCI114422. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Granger D. L., Hibbs J. B., Jr, Perfect J. R., Durack D. T. Specific amino acid (L-arginine) requirement for the microbiostatic activity of murine macrophages. J Clin Invest. 1988 Apr;81(4):1129–1136. doi: 10.1172/JCI113427. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grau G. E., Taylor T. E., Molyneux M. E., Wirima J. J., Vassalli P., Hommel M., Lambert P. H. Tumor necrosis factor and disease severity in children with falciparum malaria. N Engl J Med. 1989 Jun 15;320(24):1586–1591. doi: 10.1056/NEJM198906153202404. [DOI] [PubMed] [Google Scholar]
- Green L. C., Wagner D. A., Glogowski J., Skipper P. L., Wishnok J. S., Tannenbaum S. R. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem. 1982 Oct;126(1):131–138. doi: 10.1016/0003-2697(82)90118-x. [DOI] [PubMed] [Google Scholar]
- Green S. J., Mellouk S., Hoffman S. L., Meltzer M. S., Nacy C. A. Cellular mechanisms of nonspecific immunity to intracellular infection: cytokine-induced synthesis of toxic nitrogen oxides from L-arginine by macrophages and hepatocytes. Immunol Lett. 1990 Aug;25(1-3):15–19. doi: 10.1016/0165-2478(90)90083-3. [DOI] [PubMed] [Google Scholar]
- Green S. J., Meltzer M. S., Hibbs J. B., Jr, Nacy C. A. Activated macrophages destroy intracellular Leishmania major amastigotes by an L-arginine-dependent killing mechanism. J Immunol. 1990 Jan 1;144(1):278–283. [PubMed] [Google Scholar]
- Gryglewski R. J., Palmer R. M., Moncada S. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature. 1986 Apr 3;320(6061):454–456. doi: 10.1038/320454a0. [DOI] [PubMed] [Google Scholar]
- Hibbs J. B., Jr, Taintor R. R., Vavrin Z., Rachlin E. M. Nitric oxide: a cytotoxic activated macrophage effector molecule. Biochem Biophys Res Commun. 1988 Nov 30;157(1):87–94. doi: 10.1016/s0006-291x(88)80015-9. [DOI] [PubMed] [Google Scholar]
- Incze K., Farkas J., Mihályi V., Zukál E. Antibacterial effect of cysteine-nitrosothiol and possible percursors thereof. Appl Microbiol. 1974 Jan;27(1):202–205. doi: 10.1128/am.27.1.202-205.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Iyengar R., Stuehr D. J., Marletta M. A. Macrophage synthesis of nitrite, nitrate, and N-nitrosamines: precursors and role of the respiratory burst. Proc Natl Acad Sci U S A. 1987 Sep;84(18):6369–6373. doi: 10.1073/pnas.84.18.6369. [DOI] [PMC free article] [PubMed] [Google Scholar]
- James S. L., Glaven J. Macrophage cytotoxicity against schistosomula of Schistosoma mansoni involves arginine-dependent production of reactive nitrogen intermediates. J Immunol. 1989 Dec 15;143(12):4208–4212. [PubMed] [Google Scholar]
- Kemp D. J., Coppel R. L., Cowman A. F., Saint R. B., Brown G. V., Anders R. F. Expression of Plasmodium falciparum blood-stage antigens in Escherichia coli: detection with antibodies from immune humans. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3787–3791. doi: 10.1073/pnas.80.12.3787. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kern P., Hemmer C. J., Van Damme J., Gruss H. J., Dietrich M. Elevated tumor necrosis factor alpha and interleukin-6 serum levels as markers for complicated Plasmodium falciparum malaria. Am J Med. 1989 Aug;87(2):139–143. doi: 10.1016/s0002-9343(89)80688-6. [DOI] [PubMed] [Google Scholar]
- Kilbourn R. G., Belloni P. Endothelial cell production of nitrogen oxides in response to interferon gamma in combination with tumor necrosis factor, interleukin-1, or endotoxin. J Natl Cancer Inst. 1990 May 2;82(9):772–776. doi: 10.1093/jnci/82.9.772. [DOI] [PubMed] [Google Scholar]
- Krasna A. I., Rittenberg D. THE INHIBITION OF HYDROGENASE BY NITRIC OXIDE. Proc Natl Acad Sci U S A. 1954 Apr;40(4):225–227. doi: 10.1073/pnas.40.4.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kwiatkowski D., Hill A. V., Sambou I., Twumasi P., Castracane J., Manogue K. R., Cerami A., Brewster D. R., Greenwood B. M. TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria. Lancet. 1990 Nov 17;336(8725):1201–1204. doi: 10.1016/0140-6736(90)92827-5. [DOI] [PubMed] [Google Scholar]
- Liew F. Y., Millott S., Parkinson C., Palmer R. M., Moncada S. Macrophage killing of Leishmania parasite in vivo is mediated by nitric oxide from L-arginine. J Immunol. 1990 Jun 15;144(12):4794–4797. [PubMed] [Google Scholar]
- Lytle C. D., Ginoza W. Intracellular development of bacteriophage phi X174 inactivated by gamma-ray, ultraviolet light, or nitrous acid. Virology. 1969 May;38(1):152–165. doi: 10.1016/0042-6822(69)90138-x. [DOI] [PubMed] [Google Scholar]
- Marletta M. A., Yoon P. S., Iyengar R., Leaf C. D., Wishnok J. S. Macrophage oxidation of L-arginine to nitrite and nitrate: nitric oxide is an intermediate. Biochemistry. 1988 Nov 29;27(24):8706–8711. doi: 10.1021/bi00424a003. [DOI] [PubMed] [Google Scholar]
- McCall T. B., Boughton-Smith N. K., Palmer R. M., Whittle B. J., Moncada S. Synthesis of nitric oxide from L-arginine by neutrophils. Release and interaction with superoxide anion. Biochem J. 1989 Jul 1;261(1):293–296. doi: 10.1042/bj2610293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moore G. E., Gerner R. E., Franklin H. A. Culture of normal human leukocytes. JAMA. 1967 Feb 20;199(8):519–524. [PubMed] [Google Scholar]
- Moran D. M., Tannenbaum S. R., Archer M. C. Inhibitor of Clostridium perfringens formed by heating sodium nitrite in a chemically defined medium. Appl Microbiol. 1975 Nov;30(5):838–843. doi: 10.1128/am.30.5.838-843.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Myers P. R., Minor R. L., Jr, Guerra R., Jr, Bates J. N., Harrison D. G. Vasorelaxant properties of the endothelium-derived relaxing factor more closely resemble S-nitrosocysteine than nitric oxide. Nature. 1990 May 10;345(6271):161–163. doi: 10.1038/345161a0. [DOI] [PubMed] [Google Scholar]
- Nüssler A., Drapier J. C., Rénia L., Pied S., Miltgen F., Gentilini M., Mazier D. L-arginine-dependent destruction of intrahepatic malaria parasites in response to tumor necrosis factor and/or interleukin 6 stimulation. Eur J Immunol. 1991 Jan;21(1):227–230. doi: 10.1002/eji.1830210134. [DOI] [PubMed] [Google Scholar]
- Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
- Rockett K. A., Targett G. A., Playfair J. H. Killing of blood-stage Plasmodium falciparum by lipid peroxides from tumor necrosis serum. Infect Immun. 1988 Dec;56(12):3180–3183. doi: 10.1128/iai.56.12.3180-3183.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SHANK J. L., SILLIKER J. H., HARPER R. H. The effect of nitric oxide on bacteria. Appl Microbiol. 1962 May;10:185–189. doi: 10.1128/am.10.3.185-189.1962. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Salvemini D., Masini E., Anggard E., Mannaioni P. F., Vane J. Synthesis of a nitric oxide-like factor from L-arginine by rat serosal mast cells: stimulation of guanylate cyclase and inhibition of platelet aggregation. Biochem Biophys Res Commun. 1990 Jun 15;169(2):596–601. doi: 10.1016/0006-291x(90)90372-t. [DOI] [PubMed] [Google Scholar]
- Sethi K. K. Contribution of macrophage arginase in the intrinsic restriction of herpes simplex virus replication in permissive macrophage cultures induced by gamma-interferon containing products of activated spleen cells. Immunobiology. 1983 Dec;165(5):459–474. doi: 10.1016/S0171-2985(83)80069-2. [DOI] [PubMed] [Google Scholar]
- Stuehr D. J., Marletta M. A. Induction of nitrite/nitrate synthesis in murine macrophages by BCG infection, lymphokines, or interferon-gamma. J Immunol. 1987 Jul 15;139(2):518–525. [PubMed] [Google Scholar]
- Stuehr D. J., Marletta M. A. Mammalian nitrate biosynthesis: mouse macrophages produce nitrite and nitrate in response to Escherichia coli lipopolysaccharide. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7738–7742. doi: 10.1073/pnas.82.22.7738. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stuehr D. J., Nathan C. F. Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J Exp Med. 1989 May 1;169(5):1543–1555. doi: 10.1084/jem.169.5.1543. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tayeh M. A., Marletta M. A. Macrophage oxidation of L-arginine to nitric oxide, nitrite, and nitrate. Tetrahydrobiopterin is required as a cofactor. J Biol Chem. 1989 Nov 25;264(33):19654–19658. [PubMed] [Google Scholar]
- Trager W., Jensen J. B. Human malaria parasites in continuous culture. Science. 1976 Aug 20;193(4254):673–675. doi: 10.1126/science.781840. [DOI] [PubMed] [Google Scholar]
- Wallace W. J., Caughey W. S. Mechanism for the autoxidation of hemoglobin by phenols, nitrite and "oxidant" drugs. Peroxide formation by one electron donation to bound dioxygen. Biochem Biophys Res Commun. 1975 Feb 3;62(3):561–567. doi: 10.1016/0006-291x(75)90435-0. [DOI] [PubMed] [Google Scholar]
- Westenberger U., Thanner S., Ruf H. H., Gersonde K., Sutter G., Trentz O. Formation of free radicals and nitric oxide derivative of hemoglobin in rats during shock syndrome. Free Radic Res Commun. 1990;11(1-3):167–178. doi: 10.3109/10715769009109680. [DOI] [PubMed] [Google Scholar]