The Journal of Immunology, Vol 155, Issue 11 5306-5313, Copyright © 1995 by American Association of Immunologists

ARTICLES

Nitric oxide expression in the spleen, but not in the liver, correlates with resistance to blood-stage malaria in mice

P Jacobs, D Radzioch and MM Stevenson
Institute of Parasitology, McGill University, Ste. Anne de Bellevue, Quebec, Canada.

The production and function of nitric oxide during the early phase of blood-stage infection with Plasmodium chabaudi AS was analyzed using two inbred strains of mice that differ in the level of resistance to this parasite. Northern blot analysis of in vivo expression of inducible nitric oxide synthase (iNOS) revealed that early during infection resistant C57BL/6 mice, which clear the infection by 4 wk, have higher levels of iNOS mRNA in the spleen than susceptible A/J mice. In contrast, susceptible A/J mice have significantly increased levels of iNOS mRNA in the liver later in the course of infection just before death occurs. Splenic macrophages recovered from resistant C57BL/6 mice on day 7 postinfection express iNOS mRNA which is up- regulated following overnight stimulation of the cells with LPS. Furthermore, during the first week postinfection, splenic macrophages recovered from resistant hosts produce significantly higher levels of nitrite (NO2-) in vitro in response to LPS than similarly stimulated macrophages from susceptible A/J mice. Increased levels of nitrate (NO3- ) were only detected in serum of resistant C57BL/6 mice at the time of peak parasitemia. Treatment with the iNOS inhibitor, aminoguanidine, reduced NO3- levels in serum of C57BL/6 mice and eliminated resistance of these hosts to P. chabaudi AS malaria without affecting parasitemia. These results demonstrate that the ability to produce high amounts of nitric oxide (NO) early during infection with blood-stage P. chabaudi AS correlates with resistance, but that NO may not be involved in parasite killing. Moreover, the tissue site of NO production, that is, spleen vs liver, appears to be critical and correlates with resistance vs susceptibility to P. chabaudi AS malaria, respectively.

This article has been cited by other articles:

				J. Poovassery and J. M. Moore Murine Malaria Infection Induces Fetal Loss Associated with Accumulation of Plasmodium chabaudi AS-Infected Erythrocytes in the Placenta. Infect. Immun., May 1, 2006; 74(5): 2839 - 2848. [Abstract] [Full Text] [PDF]

				S. M. Potter, A. J. Mitchell, W. B. Cowden, L. A. Sanni, M. Dinauer, J. B. de Haan, and N. H. Hunt Phagocyte-Derived Reactive Oxygen Species Do Not Influence the Progression of Murine Blood-Stage Malaria Infections Infect. Immun., August 1, 2005; 73(8): 4941 - 4947. [Abstract] [Full Text] [PDF]

				C. S. Boutlis, J. B. Weinberg, J. Baker, M. J. Bockarie, C. S. Mgone, Q. Cheng, and N. M. Anstey Nitric Oxide Production and Nitric Oxide Synthase Activity in Malaria-Exposed Papua New Guinean Children and Adults Show Longitudinal Stability and No Association with Parasitemia Infect. Immun., December 1, 2004; 72(12): 6932 - 6938. [Abstract] [Full Text] [PDF]

				C. S. Boutlis, E. Tjitra, H. Maniboey, M. A. Misukonis, J. R. Saunders, S. Suprianto, J. B. Weinberg, and N. M. Anstey Nitric Oxide Production and Mononuclear Cell Nitric Oxide Synthase Activity in Malaria-Tolerant Papuan Adults Infect. Immun., July 1, 2003; 71(7): 3682 - 3689. [Abstract] [Full Text] [PDF]

				H. C. van der Heyde, Y. Gu, Q. Zhang, G. Sun, and M. B. Grisham Nitric Oxide Is Neither Necessary Nor Sufficient for Resolution of Plasmodium chabaudi Malaria in Mice J. Immunol., September 15, 2000; 165(6): 3317 - 3323. [Abstract] [Full Text] [PDF]

				Z. Su and M. M. Stevenson Central Role of Endogenous Gamma Interferon in Protective Immunity against Blood-Stage Plasmodium chabaudi AS Infection Infect. Immun., August 1, 2000; 68(8): 4399 - 4406. [Abstract] [Full Text] [PDF]

				A. P. Gobert, S. Daulouede, M. Lepoivre, J. L. Boucher, B. Bouteille, A. Buguet, R. Cespuglio, B. Veyret, and P. Vincendeau L-Arginine Availability Modulates Local Nitric Oxide Production and Parasite Killing in Experimental Trypanosomiasis Infect. Immun., August 1, 2000; 68(8): 4653 - 4657. [Abstract] [Full Text] [PDF]

				R. S.-P. Tan, C. Feng, Y. Asano, and A. U. Kara Altered Immune Response of Interferon Regulatory Factor 1-Deficient Mice against Plasmodium berghei Blood-Stage Malaria Infection Infect. Immun., May 1, 1999; 67(5): 2277 - 2283. [Abstract] [Full Text] [PDF]

				T. Yoneto, T. Yoshimoto, C.-R. Wang, Y. Takahama, M. Tsuji, S. Waki, and H. Nariuchi 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., May 1, 1999; 67(5): 2349 - 2356. [Abstract] [Full Text] [PDF]

				H. Sam, Z. Su, and M. M. Stevenson Deficiency in Tumor Necrosis Factor Alpha Activity Does Not Impair Early Protective Th1 Responses against Blood-Stage Malaria Infect. Immun., May 1, 1999; 67(5): 2660 - 2664. [Abstract] [Full Text] [PDF]

				H. Helmby, M. Kullberg, and M. Troye-Blomberg Altered Immune Responses in Mice with Concomitant Schistosoma mansoni and Plasmodium chabaudi Infections Infect. Immun., November 1, 1998; 66(11): 5167 - 5174. [Abstract] [Full Text] [PDF]

				S. Matsumoto, H. Yukitake, H. Kanbara, and T. Yamada Recombinant Mycobacterium bovis Bacillus Calmette-Guerin Secreting Merozoite Surface Protein 1 (MSP1) Induces Protection against Rodent Malaria Parasite Infection Depending on MSP1-stimulated Interferon gamma  and Parasite-specific Antibodies J. Exp. Med., September 7, 1998; 188(5): 845 - 854. [Abstract] [Full Text] [PDF]

				T. Yoshimoto, Y. Takahama, C.-R. Wang, T. Yoneto, S. Waki, and H. Nariuchi A Pathogenic Role of IL-12 in Blood-Stage Murine Malaria Lethal Strain Plasmodium berghei NK65 Infection J. Immunol., June 1, 1998; 160(11): 5500 - 5505. [Abstract] [Full Text] [PDF]