Skip to main content
Top
Published in: European Journal of Nutrition 3/2014

01-04-2014 | Original Contribution

Fucoxanthin in association with Vitamin c acts as modulators of human neutrophil function

Authors: A. C. Morandi, N. Molina, B. A. Guerra, A. P. Bolin, R. Otton

Published in: European Journal of Nutrition | Issue 3/2014

Login to get access

Abstract

Introduction

Neutrophils provide the first line of defense of the innate immune system by phagocytosing, killing and digesting bacteria and fungi. During this process, neutrophils produce reactive oxygen species (ROS), which in excess, can damage the cells themselves and surrounding tissues. The carotenoid fucoxanthin (Fc) has been studied concerning its antioxidant and anti-inflammatory actions. Vitamin c (Vc) also demonstrates potent antioxidant action. This study aimed to evaluate the effect of Fc (2 μM) in association with Vc (100 μM) on functional parameters of human neutrophils in vitro.

Materials and methods

We evaluated the migration and phagocytic capacity, intracellular calcium mobilization, ROS production (O 2 ·− , H2O2, HOCl), myeloperoxidase activity, profile of antioxidant enzymes, phosphorylation of p38 MAPK and p65 NFκB subunit, GSH/GSSG ratio and release of pro-inflammatory cytokines (TNF-α and IL-6) in neutrophils under different stimuli.

Results

We verified an increase in phagocytic capacity for all treatments, together with an increase in intracellular calcium only in cells treated with Fc and Fc + Vc. ROS production was reduced by all treatments, although Vc was a better antioxidant than Fc. Phosphorylation of the p-65 subunit of NFκB was reduced in cells treated with Fc + Vc and release of TNF-α and IL-6 was reduced by all treatments. These findings indicate that the regulation of inflammatory cytokines by neutrophils is not exclusively under the control of the NFκB pathway. Fc reduced the activity of some antioxidant enzymes, whereas Vc increased GR activity and the GSH/GSSG ratio.

Conclusion

In conclusion, the results presented in this study clearly show an immunomodulatory effect of the carotenoid fc alone or in combination with Vc on the function of human neutrophils.
Literature
3.
go back to reference Babior BM (1999) NADPH oxidase: an update. Blood 93(5):1464–1476 Babior BM (1999) NADPH oxidase: an update. Blood 93(5):1464–1476
4.
go back to reference Chapman AL, Hampton MB, Senthilmohan R, Winterbourn CC, Kettle AJ (2002) Chlorination of bacterial and neutrophil proteins during phagocytosis and killing of Staphylococcus aureus. J Biol Chem 277(12):9757–9762. doi:10.1074/jbc.M106134200 CrossRef Chapman AL, Hampton MB, Senthilmohan R, Winterbourn CC, Kettle AJ (2002) Chlorination of bacterial and neutrophil proteins during phagocytosis and killing of Staphylococcus aureus. J Biol Chem 277(12):9757–9762. doi:10.​1074/​jbc.​M106134200 CrossRef
5.
go back to reference Halliwell B (2001) Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment. Drugs Aging 18(9):685–716CrossRef Halliwell B (2001) Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment. Drugs Aging 18(9):685–716CrossRef
6.
go back to reference Jakus Z, Simon E, Frommhold D, Sperandio M, Mocsai A (2009) Critical role of phospholipase Cgamma2 in integrin and Fc receptor-mediated neutrophil functions and the effector phase of autoimmune arthritis. J Exp Med 206(3):577–593. doi:10.1084/jem.20081859 CrossRef Jakus Z, Simon E, Frommhold D, Sperandio M, Mocsai A (2009) Critical role of phospholipase Cgamma2 in integrin and Fc receptor-mediated neutrophil functions and the effector phase of autoimmune arthritis. J Exp Med 206(3):577–593. doi:10.​1084/​jem.​20081859 CrossRef
8.
go back to reference Biasi D, Carletto A, Caramaschi P, Bonella F, Bambara V, Pacor ML, Bambara LM (2003) Neutrophils in rheumatoid inflammation. Recenti Prog Med 94(1):25–30 Biasi D, Carletto A, Caramaschi P, Bonella F, Bambara V, Pacor ML, Bambara LM (2003) Neutrophils in rheumatoid inflammation. Recenti Prog Med 94(1):25–30
11.
go back to reference Ames BN, Shigenaga MK, Hagen TM (1993) Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 90(17):7915–7922CrossRef Ames BN, Shigenaga MK, Hagen TM (1993) Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA 90(17):7915–7922CrossRef
12.
go back to reference Fitch PM, Roghanian A, Howie SE, Sallenave JM (2006) Human neutrophil elastase inhibitors in innate and adaptive immunity. Biochem Soc Trans 34(Pt 2):279–282. doi:10.1042/BST20060279 Fitch PM, Roghanian A, Howie SE, Sallenave JM (2006) Human neutrophil elastase inhibitors in innate and adaptive immunity. Biochem Soc Trans 34(Pt 2):279–282. doi:10.​1042/​BST20060279
14.
go back to reference Sachindra NM, Sato E, Maeda H, Hosokawa M, Niwano Y, Kohno M, Miyashita K (2007) Radical scavenging and singlet oxygen quenching activity of marine carotenoid fucoxanthin and its metabolites. J Agric Food Chem 55(21):8516–8522. doi:10.1021/jf071848a CrossRef Sachindra NM, Sato E, Maeda H, Hosokawa M, Niwano Y, Kohno M, Miyashita K (2007) Radical scavenging and singlet oxygen quenching activity of marine carotenoid fucoxanthin and its metabolites. J Agric Food Chem 55(21):8516–8522. doi:10.​1021/​jf071848a CrossRef
15.
go back to reference Urikura I, Sugawara T, Hirata T (2011) Protective effect of Fucoxanthin against UVB-induced skin photoaging in hairless mice. Biosci Biotechnol Biochem 75(4):757–760CrossRef Urikura I, Sugawara T, Hirata T (2011) Protective effect of Fucoxanthin against UVB-induced skin photoaging in hairless mice. Biosci Biotechnol Biochem 75(4):757–760CrossRef
18.
19.
go back to reference Guerra BA, Bolin AP, Morandi AC, Otton R (2012) Glycolaldehyde impairs neutrophil biochemical parameters by an oxidative and calcium-dependent mechanism–protective role of antioxidants astaxanthin and vitamin C. Diabetes Res Clin Pract 98(1):108–118. doi:10.1016/j.diabres.2012.07.004 CrossRef Guerra BA, Bolin AP, Morandi AC, Otton R (2012) Glycolaldehyde impairs neutrophil biochemical parameters by an oxidative and calcium-dependent mechanism–protective role of antioxidants astaxanthin and vitamin C. Diabetes Res Clin Pract 98(1):108–118. doi:10.​1016/​j.​diabres.​2012.​07.​004 CrossRef
20.
21.
go back to reference Sampaio SC, Sousa-e-Silva MC, Borelli P, Curi R, Cury Y (2001) Crotalus durissus terrificus snake venom regulates macrophage metabolism and function. J Leukoc Biol 70(4):551–558 Sampaio SC, Sousa-e-Silva MC, Borelli P, Curi R, Cury Y (2001) Crotalus durissus terrificus snake venom regulates macrophage metabolism and function. J Leukoc Biol 70(4):551–558
24.
go back to reference Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2 + indicators with greatly improved fluorescence properties. J Biol Chem 260(6):3440–3450 Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2 + indicators with greatly improved fluorescence properties. J Biol Chem 260(6):3440–3450
25.
go back to reference Pick E, Mizel D (1981) Rapid microassays for the measurement of superoxide and hydrogen peroxide production by macrophages in culture using an automatic enzyme immunoassay reader. J Immunol Methods 46(2):211–226CrossRef Pick E, Mizel D (1981) Rapid microassays for the measurement of superoxide and hydrogen peroxide production by macrophages in culture using an automatic enzyme immunoassay reader. J Immunol Methods 46(2):211–226CrossRef
28.
29.
go back to reference Carlberg I, Mannervik B (1985) Glutathione reductase. Methods Enzymol 113:484–490CrossRef Carlberg I, Mannervik B (1985) Glutathione reductase. Methods Enzymol 113:484–490CrossRef
30.
go back to reference Rahman I, Kode A, Biswas SK (2006) Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat Protoc 1(6):3159–3165. doi:10.1038/nprot.2006.378 CrossRef Rahman I, Kode A, Biswas SK (2006) Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat Protoc 1(6):3159–3165. doi:10.​1038/​nprot.​2006.​378 CrossRef
31.
go back to reference Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254CrossRef Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254CrossRef
32.
go back to reference Bokoch GM (1995) Chemoattractant signaling and leukocyte activation. Blood 86(5):1649–1660 Bokoch GM (1995) Chemoattractant signaling and leukocyte activation. Blood 86(5):1649–1660
35.
go back to reference Guerra BA, Otton R (2011) Impact of the carotenoid astaxanthin on phagocytic capacity and ROS/RNS production of human neutrophils treated with free fatty acids and high glucose. Int Immunopharmacol 11(12):2220–2226. doi:10.1016/j.intimp.2011.10.004 CrossRef Guerra BA, Otton R (2011) Impact of the carotenoid astaxanthin on phagocytic capacity and ROS/RNS production of human neutrophils treated with free fatty acids and high glucose. Int Immunopharmacol 11(12):2220–2226. doi:10.​1016/​j.​intimp.​2011.​10.​004 CrossRef
37.
38.
go back to reference Kettle AJ, Gedye CA, Winterbourn CC (1993) Superoxide is an antagonist of antiinflammatory drugs that inhibit hypochlorous acid production by myeloperoxidase. Biochem Pharmacol 45(10):2003–2010CrossRef Kettle AJ, Gedye CA, Winterbourn CC (1993) Superoxide is an antagonist of antiinflammatory drugs that inhibit hypochlorous acid production by myeloperoxidase. Biochem Pharmacol 45(10):2003–2010CrossRef
40.
go back to reference Pullar JM, Vissers MC, Winterbourn CC (2000) Living with a killer: the effects of hypochlorous acid on mammalian cells. IUBMB Life 50(4–5):259–266. doi:10.1080/713803731 CrossRef Pullar JM, Vissers MC, Winterbourn CC (2000) Living with a killer: the effects of hypochlorous acid on mammalian cells. IUBMB Life 50(4–5):259–266. doi:10.​1080/​713803731 CrossRef
42.
go back to reference Shao B, Oda MN, Bergt C, Fu X, Green PS, Brot N, Oram JF, Heinecke JW (2006) Myeloperoxidase impairs ABCA1-dependent cholesterol efflux through methionine oxidation and site-specific tyrosine chlorination of apolipoprotein A-I. J Biol Chem 281(14):9001–9004. doi:10.1074/jbc.C600011200 CrossRef Shao B, Oda MN, Bergt C, Fu X, Green PS, Brot N, Oram JF, Heinecke JW (2006) Myeloperoxidase impairs ABCA1-dependent cholesterol efflux through methionine oxidation and site-specific tyrosine chlorination of apolipoprotein A-I. J Biol Chem 281(14):9001–9004. doi:10.​1074/​jbc.​C600011200 CrossRef
45.
go back to reference Marquez LA, Dunford HB, Van Wart H (1990) Kinetic studies on the reaction of compound II of myeloperoxidase with ascorbic acid. Role of ascorbic acid in myeloperoxidase function. J Biol Chem 265(10):5666–5670 Marquez LA, Dunford HB, Van Wart H (1990) Kinetic studies on the reaction of compound II of myeloperoxidase with ascorbic acid. Role of ascorbic acid in myeloperoxidase function. J Biol Chem 265(10):5666–5670
46.
go back to reference Marquez LA, Dunford HB (1990) Reaction of compound III of myeloperoxidase with ascorbic acid. J Biol Chem 265(11):6074–6078 Marquez LA, Dunford HB (1990) Reaction of compound III of myeloperoxidase with ascorbic acid. J Biol Chem 265(11):6074–6078
48.
go back to reference Niggli V (2003) Signaling to migration in neutrophils: importance of localized pathways. Int J Biochem Cell Biol 35(12):1619–1638CrossRef Niggli V (2003) Signaling to migration in neutrophils: importance of localized pathways. Int J Biochem Cell Biol 35(12):1619–1638CrossRef
49.
go back to reference Niggli V (2003) Microtubule-disruption-induced and chemotactic-peptide-induced migration of human neutrophils: implications for differential sets of signalling pathways. J Cell Sci 116(Pt 5):813–822CrossRef Niggli V (2003) Microtubule-disruption-induced and chemotactic-peptide-induced migration of human neutrophils: implications for differential sets of signalling pathways. J Cell Sci 116(Pt 5):813–822CrossRef
51.
go back to reference Vernooy JH, Kucukaycan M, Jacobs JA, Chavannes NH, Buurman WA, Dentener MA, Wouters EF (2002) Local and systemic inflammation in patients with chronic obstructive pulmonary disease: soluble tumor necrosis factor receptors are increased in sputum. Am J Respir Crit Care Med 166(9):1218–1224CrossRef Vernooy JH, Kucukaycan M, Jacobs JA, Chavannes NH, Buurman WA, Dentener MA, Wouters EF (2002) Local and systemic inflammation in patients with chronic obstructive pulmonary disease: soluble tumor necrosis factor receptors are increased in sputum. Am J Respir Crit Care Med 166(9):1218–1224CrossRef
52.
go back to reference Midwinter RG, Cheah FC, Moskovitz J, Vissers MC, Winterbourn CC (2006) IkappaB is a sensitive target for oxidation by cell-permeable chloramines: inhibition of NF-kappaB activity by glycine chloramine through methionine oxidation. Biochem J 396(1):71–78. doi:10.1042/BJ20052026 CrossRef Midwinter RG, Cheah FC, Moskovitz J, Vissers MC, Winterbourn CC (2006) IkappaB is a sensitive target for oxidation by cell-permeable chloramines: inhibition of NF-kappaB activity by glycine chloramine through methionine oxidation. Biochem J 396(1):71–78. doi:10.​1042/​BJ20052026 CrossRef
53.
go back to reference Kim KN, Heo SJ, Yoon WJ, Kang SM, Ahn G, Yi TH, Jeon YJ (2010) Fucoxanthin inhibits the inflammatory response by suppressing the activation of NF-kappaB and MAPKs in lipopolysaccharide-induced RAW 264.7 macrophages. Eur J Pharmacol 649(1–3):369–375. doi:10.1016/j.ejphar.2010.09.032 CrossRef Kim KN, Heo SJ, Yoon WJ, Kang SM, Ahn G, Yi TH, Jeon YJ (2010) Fucoxanthin inhibits the inflammatory response by suppressing the activation of NF-kappaB and MAPKs in lipopolysaccharide-induced RAW 264.7 macrophages. Eur J Pharmacol 649(1–3):369–375. doi:10.​1016/​j.​ejphar.​2010.​09.​032 CrossRef
54.
go back to reference Clive DR, Greene JJ (1996) Cooperation of protein disulfide isomerase and redox environment in the regulation of NF-kappaB and AP1 binding to DNA. Cell Biochem Funct 14(1):49–55. doi:10.1002/cbf.638 CrossRef Clive DR, Greene JJ (1996) Cooperation of protein disulfide isomerase and redox environment in the regulation of NF-kappaB and AP1 binding to DNA. Cell Biochem Funct 14(1):49–55. doi:10.​1002/​cbf.​638 CrossRef
55.
go back to reference Krump E, Sanghera JS, Pelech SL, Furuya W, Grinstein S (1997) Chemotactic peptide N-formyl-met-leu-phe activation of p38 mitogen-activated protein kinase (MAPK) and MAPK-activated protein kinase-2 in human neutrophils. J Biol Chem 272(2):937–944CrossRef Krump E, Sanghera JS, Pelech SL, Furuya W, Grinstein S (1997) Chemotactic peptide N-formyl-met-leu-phe activation of p38 mitogen-activated protein kinase (MAPK) and MAPK-activated protein kinase-2 in human neutrophils. J Biol Chem 272(2):937–944CrossRef
57.
58.
go back to reference Socaciu C, Jessel R, Diehl HA (2000) Carotenoid incorporation into microsomes: yields, stability and membrane dynamics. Spectrochim Acta A Mol Biomol Spectrosc 56(14):2799–2809CrossRef Socaciu C, Jessel R, Diehl HA (2000) Carotenoid incorporation into microsomes: yields, stability and membrane dynamics. Spectrochim Acta A Mol Biomol Spectrosc 56(14):2799–2809CrossRef
60.
go back to reference Gruszecki WI (1023) Sielewiesiuk J (1990) Orientation of xanthophylls in phosphatidylcholine multibilayers. Biochim Biophys Acta 3:405–412 Gruszecki WI (1023) Sielewiesiuk J (1990) Orientation of xanthophylls in phosphatidylcholine multibilayers. Biochim Biophys Acta 3:405–412
61.
go back to reference Goto S, Kogure K, Abe K, Kimata Y, Kitahama K, Yamashita E, Terada H (2001) Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin. Biochim Biophys Acta 1512(2):251–258CrossRef Goto S, Kogure K, Abe K, Kimata Y, Kitahama K, Yamashita E, Terada H (2001) Efficient radical trapping at the surface and inside the phospholipid membrane is responsible for highly potent antiperoxidative activity of the carotenoid astaxanthin. Biochim Biophys Acta 1512(2):251–258CrossRef
62.
go back to reference Barros MP, Pinto E, Colepicolo P, Pedersen M (2001) Astaxanthin and peridinin inhibit oxidative damage in Fe(2+)-loaded liposomes: scavenging oxyradicals or changing membrane permeability? Biochem Biophys Res Commun 288(1):225–232. doi:10.1006/bbrc.2001.5765 CrossRef Barros MP, Pinto E, Colepicolo P, Pedersen M (2001) Astaxanthin and peridinin inhibit oxidative damage in Fe(2+)-loaded liposomes: scavenging oxyradicals or changing membrane permeability? Biochem Biophys Res Commun 288(1):225–232. doi:10.​1006/​bbrc.​2001.​5765 CrossRef
63.
go back to reference Matsumoto M, Hosokawa M, Matsukawa N, Hagio M, Shinoki A, Nishimukai M, Miyashita K, Yajima T, Hara H (2010) Suppressive effects of the marine carotenoids, fucoxanthin and fucoxanthinol on triglyceride absorption in lymph duct-cannulated rats. Eur J Nutr 49(4):243–249. doi:10.1007/s00394-009-0078-y CrossRef Matsumoto M, Hosokawa M, Matsukawa N, Hagio M, Shinoki A, Nishimukai M, Miyashita K, Yajima T, Hara H (2010) Suppressive effects of the marine carotenoids, fucoxanthin and fucoxanthinol on triglyceride absorption in lymph duct-cannulated rats. Eur J Nutr 49(4):243–249. doi:10.​1007/​s00394-009-0078-y CrossRef
64.
go back to reference Hashimoto T, Ozaki Y, Mizuno M, Yoshida M, Nishitani Y, Azuma T, Komoto A, Maoka T, Tanino Y, Kanazawa K (2012) Pharmacokinetics of fucoxanthinol in human plasma after the oral administration of kombu extract. Br J Nutr 107(11):1566–1569. doi:10.1017/S0007114511004879 CrossRef Hashimoto T, Ozaki Y, Mizuno M, Yoshida M, Nishitani Y, Azuma T, Komoto A, Maoka T, Tanino Y, Kanazawa K (2012) Pharmacokinetics of fucoxanthinol in human plasma after the oral administration of kombu extract. Br J Nutr 107(11):1566–1569. doi:10.​1017/​S000711451100487​9 CrossRef
66.
go back to reference Bigley R, Wirth M, Layman D, Riddle M, Stankova L (1983) Interaction between glucose and dehydroascorbate transport in human neutrophils and fibroblasts. Diabetes 32(6):545–548CrossRef Bigley R, Wirth M, Layman D, Riddle M, Stankova L (1983) Interaction between glucose and dehydroascorbate transport in human neutrophils and fibroblasts. Diabetes 32(6):545–548CrossRef
67.
go back to reference Stankova L, Bigley R, Ingermann RL (1991) The effect of cyanide on vitamin C uptake by human polymorphonuclear leukocytes. Gen Pharmacol 22(5):903–905CrossRef Stankova L, Bigley R, Ingermann RL (1991) The effect of cyanide on vitamin C uptake by human polymorphonuclear leukocytes. Gen Pharmacol 22(5):903–905CrossRef
68.
go back to reference Wang Y, Russo TA, Kwon O, Chanock S, Rumsey SC, Levine M (1997) Ascorbate recycling in human neutrophils: induction by bacteria. Proc Natl Acad Sci USA 94(25):13816–13819CrossRef Wang Y, Russo TA, Kwon O, Chanock S, Rumsey SC, Levine M (1997) Ascorbate recycling in human neutrophils: induction by bacteria. Proc Natl Acad Sci USA 94(25):13816–13819CrossRef
69.
go back to reference Wolf G (1993) Uptake of ascorbic acid by human neutrophils. Nutr Rev 51(11):337–338CrossRef Wolf G (1993) Uptake of ascorbic acid by human neutrophils. Nutr Rev 51(11):337–338CrossRef
70.
go back to reference Gotoh N, Niki E (1992) Rates of interactions of superoxide with vitamin E, vitamin C and related compounds as measured by chemiluminescence. Biochim Biophys Acta 1115(3):201–207CrossRef Gotoh N, Niki E (1992) Rates of interactions of superoxide with vitamin E, vitamin C and related compounds as measured by chemiluminescence. Biochim Biophys Acta 1115(3):201–207CrossRef
71.
go back to reference Guaiquil VH, Vera JC, Golde DW (2001) Mechanism of vitamin C inhibition of cell death induced by oxidative stress in glutathione-depleted HL-60 cells. J Biol Chem 276(44):40955–40961. doi:10.1074/jbc.M106878200 CrossRef Guaiquil VH, Vera JC, Golde DW (2001) Mechanism of vitamin C inhibition of cell death induced by oxidative stress in glutathione-depleted HL-60 cells. J Biol Chem 276(44):40955–40961. doi:10.​1074/​jbc.​M106878200 CrossRef
Metadata
Title
Fucoxanthin in association with Vitamin c acts as modulators of human neutrophil function
Authors
A. C. Morandi
N. Molina
B. A. Guerra
A. P. Bolin
R. Otton
Publication date
01-04-2014
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nutrition / Issue 3/2014
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-013-0582-y

Other articles of this Issue 3/2014

European Journal of Nutrition 3/2014 Go to the issue