Lack of sensitivity to ouabain in natural killer activity

Moraes, Vera Lucia de; Olej, Beni; Rocque, Lucia de La; Rumjanek, Vivian M.

doi:10.1096/fasebj.3.12.2477295

Cited by 23 publications

(11 citation statements)

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“…Ouabain, in vitro , inhibits mitogen-induced thymocyte and lymphocyte proliferation [10, 11], inhibits the generation of lymphokine-activated killer (LAK) activity induced by IL-2 [12], increases intracellular calcium levels [13], increases CD69 expression [14] and acts both in vitro [15] and in vivo [16] synergistically with corticoids. In vitro , ouabain increases glucocorticoid-induced plasma membrane depolarization in lymphoid cells [9].…”

Section: Introductionmentioning

confidence: 99%

Anti-inflammatory and Antinociceptive Activity of Ouabain in Mice

Vasconcelos

Leite

Carneiro

et al. 2011

Mediators of Inflammation

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Ouabain, an inhibitor of the Na+/K+-ATPase pump, was identified as an endogenous substance of human plasma. Ouabain has been studied for its ability to interfere with various regulatory mechanisms. Despite the studies portraying the ability of ouabain to modulate the immune response, little is known about the effect of this substance on the inflammatory process. The aim of this work was to study the effects triggered by ouabain on inflammation and nociceptive models. Ouabain produced a reduction in the mouse paw edema induced by carrageenan, compound 48/80 and zymosan. This anti-inflammatory potential might be related to the inhibition of prostaglandin E2, bradykinin, and mast-cell degranulation but not to histamine. Ouabain also modulated the inflammation induced by concanavalin A by inhibiting cell migration. Besides that, ouabain presented antinociceptive activity. Taken these data together, this work demonstrated, for the first time, that ouabain presented in vivo analgesic and anti-inflammatory effects.

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Section: Introductionmentioning

confidence: 99%

Anti-inflammatory and Antinociceptive Activity of Ouabain in Mice

Vasconcelos

Leite

Carneiro

et al. 2011

Mediators of Inflammation

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“…Since then, a number of workers, including ourselves, has described the inhibitory effects of ouabain on lymphocyte proliferation induced by various stimuli such as mitogens (Szamel et al 1981, Moraes et al 1989, Olej et al 1998, phorbol ester (Olej et al 1994, Brodie et al 1995, CD3 (Szamel et al 1995), Interleukin-2 (Redondo et al 1986) and calcium ionophore (Jensen et al 1977).…”

Section: Introductionmentioning

confidence: 99%

Ouabain exacerbates activation-induced cell death in human peripheral blood lymphocytes

Esteves

Marques‐Santos

Affonso-Mitidieri

et al. 2005

An. Acad. Bras. Ciênc.

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Lymphocytes activated by mitogenic lectins display changes in transmembrane potential, an elevation in the cytoplasmic Ca 2+ concentrations, proliferation and/or activation induced cell death. Low concentrations of ouabain (an inhibitor of Na + ,K + -ATPase) suppress mitogen-induced proliferation and increases cell death. To understand the mechanisms involved, a number of parameters were analyzed using fluorescent probes and flow cytometry. The addition of 100nM ouabain to cultures of peripheral blood lymphocytes activated with 5µg/ml phytohemagglutinin (PHA) did not modify the increased expression of the Fas receptor or its ligand FasL induced by the mitogen. However, treatment with ouabain potentiated apoptosis induced by an anti-Fas agonist antibody. A synergy between ouabain and PHA was also observed with regard to plasma membrane depolarization. PHA per se did not induce dissipation of mitochondrial membrane potential but when cells were also exposed to ouabain a marked depolarization could be observed, and this was a late event. It is possible that the inhibitory effect of ouabain on activated peripheral blood lymphocytes involves the potentiation of some of the steps of the apoptotic process and reflects an exacerbation of the mechanism of activation-induced cell death.

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“…Since then, a number of workers, including ourselves, have described the inhibitory effects of ouabain on lymphocyte proliferation induced by various stimuli such as mitogens [135][136][137], phorbol ester [138,139], CD3 [140], calcium ionophore [141], IL-2 [142] and to a much lesser extent IL-4 [142]. It has been reported that both CD4 and CD8 lymphocytes are equally inhibited [139].…”

Section: Effect Of Ouabain On T Lymphocyte Proliferation and Activationmentioning

confidence: 99%

“…Despite inhibiting T lymphocyte proliferation, ouabain does not affect natural killer (NK) cytotoxic activity [136] nor lymphokine activated killer (LAK) [138]. However the generation of LAK cells by IL-2 or phorbol ester is inhibited by 10 -7 M ouabain [138].…”

Section: Effect Of Ouabain On T Lymphocyte Proliferation and Activationmentioning

confidence: 99%

Effect of Ouabain on the Immune System

Echevarria-Lima¹,

Rumjanek

2006

CHYR

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Immune dysfunction has been reported in patients with hypertension and in spontaneously hypertensive rats. Increased circulating levels of ouabain were observed in experimental models and in human hypertension. Despite the correlation between immunologic depression and hypertension, the mechanisms involved are unclear. This review examines evidences of immune dysfunction in hypertension and presents observations suggesting that ouabain is capable of inducing lymphocyte changes related to some of the immune disturbances observed. Defects in thymocytes, mature lymphocyte subsets, lymphocyte proliferation, cytokines balance and increased immunoglobulin production, were reported in animal models and/or hypertensive patients. Ouabain potentiates the effects of glucocorticoids on thymocytes, inducing plasma membrane depolarization, loss of mitochondrial membrane potential, changes in CD69 levels, increased intracellular calcium and apoptosis of thymocyte subsets. The activation of mature lymphocytes is inhibited by ouabain following different stimuli and these cells display changes in c-myc, CD69 and CD25 levels, plasma membrane polarization and mitochondrial membrane potential. These cells underwent apoptosis, suggesting an exacerbation of the process of activation induced cell death. Levels of cytokines such as IL-1, IL-2, IL-6, TNF, and GM-CSF are modified by ouabain. Some of the ouabain effects may result from a mechanism different from the traditional inhibition of the Na + /K + ATPase.

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Lack of sensitivity to ouabain in natural killer activity

Cited by 23 publications

References 0 publications

Anti-inflammatory and Antinociceptive Activity of Ouabain in Mice

Anti-inflammatory and Antinociceptive Activity of Ouabain in Mice

Ouabain exacerbates activation-induced cell death in human peripheral blood lymphocytes

Effect of Ouabain on the Immune System

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