Toxicity of a Soybean Oil Emulsion on Human Lymphocytes and Neutrophils

Cury-Boaventura, Maria Fernanda; Gorjão, Renata; Lima, Thaís Martins de; Piva, Tatiane Maria; Peres, Cleto Kaveski; Soriano, Francisco Garcia; Curi, Rui

doi:10.1177/0148607106030002115

Cited by 58 publications

(43 citation statements)

References 69 publications

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“…Cury-Boaventura et al (36) observed a decrease in the proliferation of lymphocytes from volunteers who received a lipid emulsion rich in LA. This effect was possibly attributable to the toxicity of the LA, whose plasma level was markedly increased.…”

Section: Discussionmentioning

confidence: 98%

Regulation of interleukin-2 signaling by fatty acids in human lymphocytes

Gorjão

Hirabara

Lima

et al. 2007

Journal of Lipid Research

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Docosahexaenoic (DHA; C22:6 n-3), eicosapentaenoic (EPA; C20:5 n-3), palmitic (PA; C16:0), and stearic (SA; C18:0) acids decrease lymphocyte proliferation in concentrations of .50 mM, as observed in our previous study. However, oleic acid (OA; C18:1 n-9) and linoleic acid (LA; C18:2 n-6) increase lymphocyte proliferation at 25 mM. In this study, the effect of these FAs on the interleukin-2 (IL-2) signaling pathway in human lymphocytes was investigated. Cells were isolated from heparinized venous blood of healthy human donors by density-gradient sedimentation. Cells were stimulated with 5 mg/ml concanavalin A and treated with FAs in the absence or presence of IL-2 for 1 hour. CD25-a externalization was analyzed by flow cytometry, and Janus kinase 1 ( JAK1), JAK3, signal transducer and activator of transcription (STAT) 5, extracellular signalregulated kinases (ERKs) 1 and 2, Akt, and protein kinase C (PKC)-Z phosphorylation were analyzed by Western blotting. The expression of CD25-a at the cell surface was increased by DHA, SA, and PA but was unaffected by EPA, OA, and LA. PA, SA, DHA, and EPA decreased JAK1, JAK3, STAT5, and Akt phosphorylation induced by IL-2, but OA and LA did not cause any effect. OA and LA increased ERK1/2 phosphorylation, whereas the other FAs caused a marked decrease. PKC-Z phosphorylation was decreased by OA and LA and was not altered by the remaining FAs. In conclusion, the inhibitory effect of PA, SA, DHA, and EPA on lymphocyte proliferation observed in our previous study was attributable to a decrease in JAK/STAT, ERK, and Akt pathways activated by IL-2. Probably, OA and LA stimulated lymphocyte proliferation by increasing ERK1/2 phosphorylation through PKC-Z activation. The inhibition of JAK1, JAK3, STAT5, ERK1/2, and Akt phosphorylation caused by DHA, SA, and PA is associated with an alteration of CD25 expression at the cell surface.-Gorjão, R., S. M. Hirabara, T. M. de Lima, M. F. Cury-Boaventura, and R. Curi. Regulation of interleukin-2 signaling by fatty acids in human lymphocytes. J. Lipid Res.

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Section: Discussionmentioning

confidence: 98%

Regulation of interleukin-2 signaling by fatty acids in human lymphocytes

Gorjão

Hirabara

Lima

et al. 2007

Journal of Lipid Research

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“…The time required for their incorporation is very short. In fact, some studies have shown modification in fatty acids plasma membranes composition immediately after lipid emulsion infusion (Cury-Boaventura et al, 2006). More recently, our group demonstrated that 5 days of pure linoleic acid supplementation increases the percentage of linoleic acid, without altering oleic and arachidonic acids contentes, in rat neutrophil membranes (Rodrigues et al, 2010).…”

Section: Omega 6 (N-6) Fatty Acidsmentioning

confidence: 90%

Fatty acids as modulators of neutrophil recruitment, function and survival

Rodrigues

Sato

Curi

et al. 2016

European Journal of Pharmacology

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“…In the present study, OA and LA at 25 mM raised the stimulatory effect of IL-2 on lymphocyte proliferation. Considering the fact that high concentrations of these FA induce apoptosis in various cell types, 58,59 it is suggested that OA and LA might modulate signal transduction to enhance lymphocyte proliferation at low and non-toxic concentrations, whereas higher concentrations cause apoptosis. IL-2 signalling includes STAT5a/b, ERK 1/2 and Akt activation.…”

Section: Discussionmentioning

confidence: 99%

Regulation of human lymphocyte proliferation by fatty acids

Gorjão

Cury-Boaventura

Lima

et al. 2006

Cell Biochemistry & Function

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In the present study, the effect of increasing concentrations of palmitic (PA, C16:0), stearic (SA, C18:0), oleic (OA, C18:1, n-9), linoleic (LA, C18:2n-6), docosahexaenoic (DHA, C22:6 n-3) and eicosapentaenoic (EPA, C20:5 n-3) acids on lymphocyte proliferation was investigated. The maximal non-toxic concentrations of these fatty acids for human lymphocytes in vitro were determined. It was also evaluated whether these fatty acids at non-toxic concentrations affect IL-2 induced lymphocyte proliferation and cell cycle progression. OA and LA at 25 microM increased lymphocyte proliferation and at higher concentrations (75 microM and 100 microM) inhibited it. Both fatty acids promoted cell death at 200 microM concentration. PA and SA decreased lymphocyte proliferation at 50 microM and promoted cell death at concentrations of 100 microM and above. EPA and DHA decreased lymphocyte proliferation at 25 and 50 microM being toxic at 50 and 100 microM, respectively. PA, SA, DHA and EPA decreased the stimulatory effect of IL-2 on lymphocyte proliferation, increasing the percentage of cells in G1 phase and decreasing the proportion of cells in S and G2/M phases. OA and LA caused an even greater pronounced effect. The treatment with all fatty acids increased neutral lipid accumulation in the cells but the effect was more pronounced with PA and DHA. In conclusion, PA, SA, DHA and EPA decreased lymphocyte proliferation, whereas OA and LA stimulated it at non-toxic concentrations.

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Toxicity of a Soybean Oil Emulsion on Human Lymphocytes and Neutrophils

Abstract: Soybean oil emulsion given as a single dose of 500 mL promotes lymphocyte and neutrophil death that may enhance the susceptibility of the patients to infections.

Cited by 58 publications

References 69 publications

Regulation of interleukin-2 signaling by fatty acids in human lymphocytes

Regulation of interleukin-2 signaling by fatty acids in human lymphocytes

Fatty acids as modulators of neutrophil recruitment, function and survival

Regulation of human lymphocyte proliferation by fatty acids

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