Nitric oxide-induced apoptotic cell death in the acute phase of Trypanosoma cruzi infection in mice

Martins, Gislâine A.; Cardoso, Maria Angélica Gargione; Aliberti, Júlio; Silva, João

doi:10.1016/s0165-2478(98)00066-2

Cited by 92 publications

(80 citation statements)

References 33 publications

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“…A causal role for TNF in induction of NO is clearly shown, although the exclusive involvement of the cell-associated and not the secreted form of TNF has not been addressed in the work of others. In all examples referenced herein, IFN-␥ synergizes with TNF to induce NO, which is the mediator of target cell death, including murine cardiac cells (52), rat mesangial cells (53), rat (54) and murine (55) endothelial cells, human (56) and murine (57) tumor cell lines, murine splenocytes in vivo after infection of host macrophages with T. cruzi (58), and macrophage cell lines when infected with various pathogens (Pneumocystis carinii (59), Leishmania major (60), and Klebsiella pneumonia (61)). The role of NO in induction of target cell apoptosis is likely species-specific in that, in general, normal human cells in culture are protected from cell TNF-mediated cell death by NO including endothelia (62), smooth muscle (63), and liver (64).…”

Section: Discussionmentioning

confidence: 99%

Tumor-Infiltrating Macrophages Induce Apoptosis in Activated CD8+ T Cells by a Mechanism Requiring Cell Contact and Mediated by Both the Cell-Associated Form of TNF and Nitric Oxide

Saio

Radoja

Marino

et al. 2001

The Journal of Immunology

141

106

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We have investigated the ability of different cells present in murine tumors to induce apoptosis of activated CD8+ T cells in vitro. Tumor cells do not induce apoptosis of T cells; however, macrophages that infiltrate tumors are potent inducers of apoptosis. Tumor macrophages express cell surface-associated TNF, TNF type I (CD120a) and II (CD120b) receptors, and, upon contact with T cells which induces release of IFN-γ from T cells, secrete nitric oxide. Killing of T cells in vitro is blocked by Abs to IFN-γ, TNF, CD120a, or CD120b, or N-methyl-l-arginine. In concert with that finding, tumor macrophages isolated from either TNF type I or type II receptor −/− mice are not proapoptotic and do not produce nitric oxide upon contact with activated T cells. Control macrophages do not express TNF receptors or release nitric oxide. Tumor cells or tumor-derived macrophages do not express FasL, and blocking Abs to either Fas or FasL have no effect on macrophage-mediated T cell killing. These results demonstrate that macrophages which infiltrate tumors are highly proapoptotic and may be responsible for elimination of activated antitumor T cells within the tumor bed.

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Section: Discussionmentioning

confidence: 99%

Tumor-Infiltrating Macrophages Induce Apoptosis in Activated CD8+ T Cells by a Mechanism Requiring Cell Contact and Mediated by Both the Cell-Associated Form of TNF and Nitric Oxide

Saio

Radoja

Marino

et al. 2001

The Journal of Immunology

141

106

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“…51 For example, macrophage-derived NO plays a role in apoptosis of splenocytes during the acute phase of experimental Trypanosoma cruzi infection, supporting the notion that immunosuppression and apoptosis are to be correlated under certain in vivo situations. 52 iNOS-generated NO evoked apoptosis in ascites hepatoma cells under in vivo conditions in tumor-bearing rats 53 and NO caused autolysis in tumor cells and lysed bystander cells under in vitro and in vivo conditions. 54 Moreover, macrophages from septic mice exhibited increased apoptosis that was blocked by NOSinhibition.…”

Section: Lessons From Disease Statesmentioning

confidence: 98%

Nitric oxide (NO): an effector of apoptosis

1999

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It is appreciated that the production of nitric oxide (NO) from Larginine metabolism is an essential determinate of the innate immune system, important for nonspecific host defense, as well as tumor and pathogen killing. Cytotoxicity as a result of a substantial NO-formation is established to initiate apoptosis, characterized by upregulation of the tumor suppressor p53, changes in the expression of pro-and anti-apoptotic Bcl-2 family members, cytochrome c relocation, activation of caspases, chromatin condensation, and DNA fragmentation. Proof for the involvement of NO was demonstrated by blocking adverse effects by NO-synthase inhibition. However, NOtoxicity is not a constant value and NO may achieve cell protection as well. In part this is understood by transcription and translation of protective proteins, such as cyclooxygenase-2. Alternatively, protection may result as a consequence of a diffusion controlled NO/O 2 7 (superoxide) interaction that redirects the apoptotic initiating activity of NO towards protection. NO is endowed with the unique ability to initiate and to block apoptosis, depending on multiple variables that exist to be elucidated. The crosstalk between cell destructive and protective signaling pathways under the modulatory influence of NO will determine the impact of NO in apoptotic cell death and survival.

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“…Several investigators have utilized mice treated with antibody to immune mediators and murine models in which genes for various immune mediators have been deleted to evaluate the signifi cance of inflammatory response in chagasic disease. These include mice defi cient in inducible NO synthase (iNOS), IFN-γ , TNF-α, TNF-α receptor, and CD4 + and/or CD8 + T cells (Minoprio et al 1987, Tarleton 1990, Tarleton et al 1992, Bachmaier et al 1997, Martins et al 1998, Aliberti et al 2001, Chandra et al 2002. The overall observation from these studies is that despite a general increase in parasite burden, the extent of cell death and tissue damage are diminished in mice defi cient in inflam-matory mediators compared to the wild-type controls, thus suggesting the pathological signifi cance of persistent inflammation in chagasic disease.…”

Section: Experimental Studiesmentioning

confidence: 99%

“…T. cruzi elicits IFN-γ production by NK cells, activating Mφ (Torrico et al 1991, Gazzinelli et al 1992. In turn, Mφ produce TNF-α, inducing nitric oxide (NO), which is toxic to parasites in vitro (Vespa et al 1994, Martins et al 1998). Interestingly, GPI-anchored macromolecules, abundantly expressed by the infective and intracellular stages of the parasite, have been characterized as the prime inducers of the proinflammatory cytokines (e.g.…”

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confidence: 99%

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An overview of chagasic cardiomyopathy: pathogenic importance of oxidative stress

Zacks

Wen

Vyatkina

et al. 2005

An. Acad. Bras. Ciênc.

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There is growing evidence to suggest that chagasic myocardia are exposed to sustained oxidative stressinduced injuries that may contribute to disease progression. Pathogen invasion-and replication-mediated cellular injuries and immune-mediated cytotoxic reactions are the common source of reactive oxygen species (ROS) in infectious etiologies. However, our understanding of the source and role of oxidative stress in chagasic cardiomyopathy (CCM) remains incomplete. In this review, we discuss the evidence for increased oxidative stress in chagasic disease, with emphasis on mitochondrial abnormalities, electron transport chain dysfunction and its role in sustaining oxidative stress in myocardium. We discuss the literature reporting the consequences of sustained oxidative stress in CCM pathogenesis.Key words: chagasic cardiomyopathy, reactive oxygen species, inflammation, mitochondria, oxidant/antioxidant status, oxidative damage. PARASITE, VECTOR AND TRANSMISSIONTrypanosoma cruzi, a parasitic protozoan of the ancient branch of eukaryotes (Kingdom Eukaryota, Order Kinetoplastida), is the etiological agent of Chagas disease in humans (Miles 2003). Currently, the World Health Organization estimates that 11-18 million individuals are infected worldwide (WHO 2002). Transmission of T. cruzi occurs predominantly via insect vectors of the subfamily Triatoma, family Reduviidae, referred to as " kissing bugs". Residing in the peridomestic habitat of mud-thatch Correspondence to: Nisha Garg Ph.D. E-mail: nigarg@utmb.edu houses in rural areas (Mott et al. 1978), Triatoma infestans in South America, Rhodnius prolixus in Venezuela, Colombia and Central America (Schofi eld and Dias 1999), and Triatoma barberi in Mexico (Guzman 2001), are the most common species responsible for transmission. Improvements in housing conditions and vector control measures instituted by the Southern Cone Initiative in 1991 have contributed to a decline in transmission in endemic countries (Schofi eld and Dias 1999). However, concern remains that reinfestation of homes by secondary sylvatic vectors, e.g. Triatoma sordida, will compromise the long-term effi cacy of vector control measures in Brazil and other Southern American countries (Monteiro et al. 2001, WHO 2002. Blood transfusion and organ transplantation represent further routes of T. cruzi transmission. Although many countries in Latin America screen blood donations for T. cruzi, infection rates ranging from 0.1% to 24.4% are estimated to occur through transfusion (WHO 2002).In the U.S., vector-transmitted human infections have been reported in the southern States (Ochs et al. 1996, Herwaldt et al. 2000. Several studies have shown the presence of the insect vector as well as infection of domestic dogs and wild animals in the US (Meurs et al. 1998, Bradley et al. 2000, Beard et al. 2003, Yabsley and Noblet 2002. Further, due to signifi cant increases in immigration to the USA and Canada from endemic countries and perinatal transmission, it is estimated that ∼ 100, 000 people residing...

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Nitric oxide-induced apoptotic cell death in the acute phase of Trypanosoma cruzi infection in mice

Cited by 92 publications

References 33 publications

Tumor-Infiltrating Macrophages Induce Apoptosis in Activated CD8+ T Cells by a Mechanism Requiring Cell Contact and Mediated by Both the Cell-Associated Form of TNF and Nitric Oxide

Tumor-Infiltrating Macrophages Induce Apoptosis in Activated CD8+ T Cells by a Mechanism Requiring Cell Contact and Mediated by Both the Cell-Associated Form of TNF and Nitric Oxide

Nitric oxide (NO): an effector of apoptosis

An overview of chagasic cardiomyopathy: pathogenic importance of oxidative stress

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