Protective and pathological roles of nitric oxide in endotoxin shock

Wright, Christine E.; Rees, Daryl D.; Moncada, Salvador

doi:10.1093/cvr/26.1.48

Cited by 581 publications

(273 citation statements)

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“…Induction of NO synthase by these cytokines is thought to be a major event in the pathogenesis of septic shock [36]. Herein, we reported that anti-CD3 MoAb induces a systemic release of NO metabolites and that the priming for IFN-and TNF-production in the course of T. cruzi infection is responsible, at least in part, for this NO overproduction.…”

Section: Discussionmentioning

confidence: 93%

Administration of anti-CD3 monoclonal antibody during experimental Chagas’ disease induces CD8+ cell-dependent lethal shock

Jacobs

Dubois

Carlier

et al. 1996

Clinical and Experimental Immunology

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SUMMARYThe injection of the 145-2C11 anti-CD3 MoAb in mice induces a polyclonal T cell activation resulting in the release of several cytokines, including interferon-gamma (IFN-) and tumour necrosis factoralpha (TNF-). As these cytokines are known to be involved in the host defence against Trypanosoma cruzi, we measured serum levels of IFN-and TNF-after injection of the 145-2C11 MoAb in the course of experimental murine Chagas' disease. Compared with control mice, T. cruzi-infected BALB/c mice were found to be primed to secrete very high levels of IFN-and TNF-from the second and the first week of infection, respectively, up to the chronic phase. In vivo cell depletion experiments indicated that CD8 T cells were responsible for these dramatic hyperproductions of IFN-and TNF-. While all control mice survived anti-CD3 MoAb injection, a high lethality rate was observed in T. cruzi-infected mice within 24 h after anti-CD3 MoAb challenge. Pretreatment with neutralizing anti-IFN-MoAb or depletion of CD8 T cell population dramatically decreased the mortality induced by anti-CD3 MoAb in T. cruzi-infected mice. Finally, we showed that anti-CD3 MoAb injection in T. cruzi-infected mice was followed by a massive release of nitric oxide (NO) metabolites, which was partially reduced by IFN-or TNF-neutralization. The administration of the NO synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) before anti-CD3 MoAb challenge did not prevent and even enhanced lethality in T. cruzi-infected mice, suggesting that NO overproduction and lethal shock are not causally related. We conclude that injection of anti-CD3 MoAb in the course of experimental Chagas' disease induces a CD8 cell-dependent shock mediated by IFN-and TNF-.

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Section: Discussionmentioning

confidence: 93%

Administration of anti-CD3 monoclonal antibody during experimental Chagas’ disease induces CD8+ cell-dependent lethal shock

Jacobs

Dubois

Carlier

et al. 1996

Clinical and Experimental Immunology

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“…A third type, inducible NOS (iNOS or type II), is induced after immunological or inflammatory stimuli with substances such as cytokines or Gram-negative bacteria. Induction of iNOS produces high output of NO 2 and has been proposed to be a major factor involved in pathologic vasodilatation and tissue damage observed in patients with and in animal models of sepsis and septic shock [3][4][5] and in side effects of antitumor therapy with cytokines. 6 Understanding the molecular mechanisms of iNOS induction may provide the fundamental basis for developing reagents to control gene activation in pathophysiological conditions.…”

Section: G Eneration Of Nitric Oxide (No) From Its Substratementioning

confidence: 99%

Nitric Oxide Differentially Regulates Induction of Type II Nitric Oxide Synthase in Rat Vascular Smooth Muscle Cells Versus Macrophages

Zhang

Snead

Catravas

2001

ATVB

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Abstract-We studied effects of nitric oxide (NO) released by different NO donors on induction of inducible NO synthase (iNOS) in rat aortic smooth muscle cells (RASMC) and rat macrophage cell line NR8383. iNOS protein expression induced by a CM (interleukin-1␤ 250 U/mL, interferon-␥ 150 U/mL, and tumor necrosis factor-␣ 150 U/mL) was not affected by the NO donor SNAP (0.2 to 1 mmol/L) in RASMC at 24 hours of incubation but was dose-dependently decreased by SNAP in macrophages (maximal 60% inhibition). A fully functional Ϫ3.2-kb rat iNOS promoter was transfected into RASMC and macrophages. The CM-induced promoter activity in transfected macrophages was inhibited by SNAP (maximal 67% inhibition), but this inhibitory effect by SNAP was not observed in transfected RASMC. Electrophoretic mobility-shift assays demonstrated that nuclear factor-B (NF-B) binding patterns were different in 2 cell types and that the ratio of p50:p65 subunits was significantly lower in macrophages than in RASMC. Furthermore, NF-B activity was not affected by SNAP in RASMC but was reduced by SNAP in macrophages. Another putative NO donor, NOR3 (1 mmol/L), completely inhibited iNOS induction by CM in RASMC, but this was accompanied by severe cytotoxicity, which resulted in cell death. Similar concentrations of SNAP did not exhibit cytotoxicity in RASMC, whereas macrophages demonstrated 88% viability compared with cells without SNAP. NO synthase inhibitor N g -monomethyl-L-arginine significantly inhibited CM-induced nitrite production in both cell types and stimulated iNOS protein expression in macrophages but did not affect iNOS expression in RASMC. These data strongly suggest that NO may affect transcriptional regulation of iNOS differently in RASMC

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“…Experimental models of endotoxin shock have shown that administration of bacterial lipopolysaccharide (LPS) to animals in vivo results in a characteristic biphasic fall in systemic blood pressure in which the first phase of the response occurs rapidly following administration of LPS and the second phase develops as a gradual progressive fall in blood pressure after a lag phase of about 30 min (Thiemermann & Vane, 1990;Wright et al, 1992). The development of the sustained hypotensive response (second phase) is currently attributed mainly to nitric oxide (NO) (Kilbourn et al, 1990;Thiemermann & Vane, 1990;Wright et al, 1992), derived from the cationic amino acid L-arginine (Palmer et al, 1988a;Schmidt et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

“…The development of the sustained hypotensive response (second phase) is currently attributed mainly to nitric oxide (NO) (Kilbourn et al, 1990;Thiemermann & Vane, 1990;Wright et al, 1992), derived from the cationic amino acid L-arginine (Palmer et al, 1988a;Schmidt et al, 1988). Synthesis of NO under these conditions involves induction of the Ca2+/calmodulinindependent NO synthase previously identified in macrophages (Stuehr & Marletta, 1987;Marletta et al, 1988).…”

Section: Introductionmentioning

confidence: 99%

“…Expression of this enzyme is time-dependent and involves de novo protein synthesis which can be inhibited by the protein synthesis inhibitor, cyclohexamide and by the glucocorticoid, dexamethasone (Knowles et al, 1990;Radomski et al, 1990;Rees et al, 1990a). Once induced the activity of the enzyme can be blocked by inhibitors of NO synthase including NGmonomethyl-L-arginine (L-NMMA) (Kilbourn et al, 1990;Radomski et al, 1990;Rees et al, 1990a;Thiemermann & Vane, 1990, Wright et al, 1992.…”

Section: Introductionmentioning

confidence: 99%

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Bacterial endotoxin rapidly stimulates prolonged endothelium‐dependent vasodilatation in the rat isolated perfused heart

Baydoun

Foale

Mann

1993

British J Pharmacology

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1 The effects of bacterial lipopolysaccharide (Escherichia coli 011 1-B4; LPS) on coronary vascular tone were examined in the isolated perfused heart of the rat. The role of nitric oxide and/or prostaglandin products of the cyclo-oxygenase pathway in mediating the actions of LPS were also investigated. 2 Coronary vascular tone was raised and maintained by a continuous perfusion of the thromboxanemimetic U46619 (5nM). LPS perfusion (0.1-100itgml-') caused a concentration-dependent fall in coronary tone without any significant change in the force of cardiac contractility.3 At 5 lggml', LPS reduced perfusion pressure by 38±9mmHg. This effect was rapid in onset, maximal within the first 5 min and sustained for 90 + 10 min (n = 6). 4 The vasodilatation induced by LPS was dependent on the presence of an intact endothelium and abolished following endothelial damage caused by air embolism.5 NW-nitro-L-arginine methylester (L-NAME; 50 gM) or N0-nitro-L-arginine (L-NOARG; 50 tM) blocked the vasodilatation induced by LPS (5 jLg ml--). The inhibition caused by these arginine analogues was partially reversed by 1 mM L-but not D-arginine. 6 The vasodilator action of LPS was also completely blocked by the glucocorticoid, dexamethasone (10 jiM) but unaffected by indomethacin (10 jiM).7 These results suggest that LPS evokes rapid release of nitric oxide (NO) in the microvasculature of the rat isolated heart presumably via activation of the constitutive L-arginine-NO pathway in the endothelium. Furthermore, the lack of effect of indomethacin suggests that prostaglandins released via the cyclo-oxygenase pathway are not involved in mediating this action of LPS.

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Protective and pathological roles of nitric oxide in endotoxin shock

Cited by 581 publications

References 0 publications

Administration of anti-CD3 monoclonal antibody during experimental Chagas’ disease induces CD8+ cell-dependent lethal shock

Administration of anti-CD3 monoclonal antibody during experimental Chagas’ disease induces CD8+ cell-dependent lethal shock

Nitric Oxide Differentially Regulates Induction of Type II Nitric Oxide Synthase in Rat Vascular Smooth Muscle Cells Versus Macrophages

Bacterial endotoxin rapidly stimulates prolonged endothelium‐dependent vasodilatation in the rat isolated perfused heart

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