Abstract
Mice infected with Trypanosoma brucei rapidly develop anemia, with the number of circulating erythrocytes reduced by 50% within a week after infection. The present study investigated the relationship between anemia and bone marrow nitric oxide (NO) production. Bone marrow cell populations from T. brucei-infected mice exhibited elevated levels of NO synthase activity which was inhibitable by NG-nitro-L-arginine methyl ester. NO production was found to coincide with suppressed bone marrow T-cell proliferation in response to stimulation with the mitogen concanavalin A both in vitro and in vivo. As this indicated that NO may inhibit proliferation in other cell types, particularly hemopoietic precursors, we examined the role of NO in anemia during trypanosome infection. NO production correlated directly with the development of anemia, and treatment of infected mice with NG-nitro-L-arginine methyl ester in vivo to systemically inhibit NO synthesis led to a significant reduction in the anemia. Thus, elevated NO production in the bone marrow of T. brucei-infected mice is likely to play a significant role in the anemia resulting from T. brucei infection.
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- Askonas B. A. Macrophages as mediators of immunosuppression in murine African trypanosomiasis. Curr Top Microbiol Immunol. 1985;117:119–127. doi: 10.1007/978-3-642-70538-0_6. [DOI] [PubMed] [Google Scholar]
- Balber A. E. Trypanosoma brucei: attenuation by cortcosteroids of the anemia of infected mice. Exp Parasitol. 1974 Apr;35(2):209–218. doi: 10.1016/0014-4894(74)90024-1. [DOI] [PubMed] [Google Scholar]
- Baltz T., Baltz D., Giroud C., Crockett J. Cultivation in a semi-defined medium of animal infective forms of Trypanosoma brucei, T. equiperdum, T. evansi, T. rhodesiense and T. gambiense. EMBO J. 1985 May;4(5):1273–1277. doi: 10.1002/j.1460-2075.1985.tb03772.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Clayton C. E., Selkirk M. E., Corsini C. A., Ogilvie B. M., Askonas B. A. Murine trypanosomiasis: cellular proliferation and functional depletion in the blood, peritoneum, and spleen related to changes in bone marrow stem cells. Infect Immun. 1980 Jun;28(3):824–831. doi: 10.1128/iai.28.3.824-831.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dargie J. D., Murray P. K., Murray M., Grimshaw W. R., McIntyre W. I. Bovine trypanosomiasis: the red cell kinetics of ndama and Zebu cattle infected with Trypanosoma congolense. Parasitology. 1979 Jun;78(3):271–286. doi: 10.1017/s0031182000051143. [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]
- Dudek R. R., Wildhirt S., Pinto V., Giesler G., Bing R. J. Dexamethasone inhibits the expression of an inducible nitric oxide synthase in infarcted rabbit myocardium. Biochem Biophys Res Commun. 1994 Jul 29;202(2):1120–1126. doi: 10.1006/bbrc.1994.2044. [DOI] [PubMed] [Google Scholar]
- Duffey L. M., Albright J. W., Albright J. F. Trypanosoma musculi: population dynamics of erythrocytes and leukocytes during the course of murine infections. Exp Parasitol. 1985 Jun;59(3):375–389. doi: 10.1016/0014-4894(85)90093-1. [DOI] [PubMed] [Google Scholar]
- Feelisch M., Noack E. A. Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase. Eur J Pharmacol. 1987 Jul 2;139(1):19–30. doi: 10.1016/0014-2999(87)90493-6. [DOI] [PubMed] [Google Scholar]
- Hudson K. M., Byner C., Freeman J., Terry R. J. Immunodepression, high IgM levels and evasion of the immune response in murine trypanosomiasis. Nature. 1976 Nov 18;264(5583):256–258. doi: 10.1038/264256a0. [DOI] [PubMed] [Google Scholar]
- Jarvinen J. A., Dalmasso A. P. Trypanosoma musculi: immunologic features of the anemia in infected mice. Exp Parasitol. 1977 Oct;43(1):203–210. doi: 10.1016/0014-4894(77)90024-8. [DOI] [PubMed] [Google Scholar]
- Kobayakawa T., Louis J., Izui S., Lambert P. H. Autoimmune response to DNA, red blood cells, and thymocyte antigens in association with polyclonal antibody synthesis during experimental African trypanosomiasis. J Immunol. 1979 Jan;122(1):296–301. [PubMed] [Google Scholar]
- Mabbott N. A., Sutherland I. A., Sternberg J. M. Trypanosoma brucei is protected from the cytostatic effects of nitric oxide under in vivo conditions. Parasitol Res. 1994;80(8):687–690. doi: 10.1007/BF00932954. [DOI] [PubMed] [Google Scholar]
- McCall T. B., Palmer R. M., Moncada S. Induction of nitric oxide synthase in rat peritoneal neutrophils and its inhibition by dexamethasone. Eur J Immunol. 1991 Oct;21(10):2523–2527. doi: 10.1002/eji.1830211032. [DOI] [PubMed] [Google Scholar]
- Mills C. D. Molecular basis of "suppressor" macrophages. Arginine metabolism via the nitric oxide synthetase pathway. J Immunol. 1991 Apr 15;146(8):2719–2723. [PubMed] [Google Scholar]
- Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
- Murray P. K., Jennings F. W., Murray M., Urquhart G. M. The nature of immunosuppression in Trypanosoma brucei infections in mice. II. The role of the T and B lymphocytes. Immunology. 1974 Nov;27(5):825–840. [PMC free article] [PubMed] [Google Scholar]
- Preston J. M., Wellde B. T., Kovatch R. M. Trypanosoma congolense: calf erythrocyte survival. Exp Parasitol. 1979 Aug;48(1):118–125. doi: 10.1016/0014-4894(79)90061-4. [DOI] [PubMed] [Google Scholar]
- Punjabi C. J., Laskin D. L., Heck D. E., Laskin J. D. Production of nitric oxide by murine bone marrow cells. Inverse correlation with cellular proliferation. J Immunol. 1992 Sep 15;149(6):2179–2184. [PubMed] [Google Scholar]
- Schleifer K. W., Mansfield J. M. Suppressor macrophages in African trypanosomiasis inhibit T cell proliferative responses by nitric oxide and prostaglandins. J Immunol. 1993 Nov 15;151(10):5492–5503. [PubMed] [Google Scholar]
- Sileghem M., Flynn J. N., Logan-Henfrey L., Ellis J. Tumour necrosis factor production by monocytes from cattle infected with Trypanosoma (Duttonella) vivax and Trypanosoma (Nannomonas) congolense: possible association with severity of anaemia associated with the disease. Parasite Immunol. 1994 Jan;16(1):51–54. doi: 10.1111/j.1365-3024.1994.tb00304.x. [DOI] [PubMed] [Google Scholar]
- Sternberg J., Mabbott N., Sutherland I., Liew F. Y. Inhibition of nitric oxide synthesis leads to reduced parasitemia in murine Trypanosoma brucei infection. Infect Immun. 1994 May;62(5):2135–2137. doi: 10.1128/iai.62.5.2135-2137.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sternberg J., McGuigan F. Nitric oxide mediates suppression of T cell responses in murine Trypanosoma brucei infection. Eur J Immunol. 1992 Oct;22(10):2741–2744. doi: 10.1002/eji.1830221041. [DOI] [PubMed] [Google Scholar]
- Thoongsuwan S., Cox H. W. Anemia, splenomegaly, and glomerulonephritis associated with autoantibody in Trypanosoma lewisi infections. J Parasitol. 1978 Aug;64(4):669–673. [PubMed] [Google Scholar]
- Van Meirvenne N., Janssens P. G., Magnus E. Antigenic variation in syringe passaged populations of Trypanosoma (Trypanozoon) brucei. 1. Rationalization of the experimental approach. Ann Soc Belg Med Trop. 1975;55(1):1–23. [PubMed] [Google Scholar]