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Erschienen in: Environmental Health and Preventive Medicine 1/2013

01.01.2013 | Short Communication

Folate-deficiency induced cell-specific changes in the distribution of lymphocytes and granulocytes in rats

verfasst von: Ikumi Abe, Ken Shirato, Yoko Hashizume, Ryosuke Mitsuhashi, Ayumu Kobayashi, Chikako Shiono, Shogo Sato, Kaoru Tachiyashiki, Kazuhiko Imaizumi

Erschienen in: Environmental Health and Preventive Medicine | Ausgabe 1/2013

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Abstract

Objective

Folate (vitamin B9) plays key roles in cell growth and proliferation through regulating the synthesis and stabilization of DNA and RNA, and its deficiency leads to lymphocytopenia and granulocytopenia. However, precisely how folate deficiency affects the distribution of a variety of white blood cell subsets, including the minor population of basophils, and the cell specificity of the effects remain unclear. Therefore, we examined the effects of a folate-deficient diet on the circulating number of lymphocyte subsets [T-lymphocytes, B-lymphocytes, and natural killer (NK) cells] and granulocyte subsets (neutrophils, eosinophils, and basophils) in rats.

Methods

Rats were divided into two groups, with one receiving the folate-deficient diet (FAD group) and the other a control diet (CON group). All rats were pair-fed for 8 weeks.

Results

Plasma folate level was dramatically lower in the FAD group than in the CON group, and the level of homocysteine in the plasma, a predictor of folate deficiency was significantly higher in the FAD group than in the CON group. The number of T-lymphocytes, B-lymphocytes, and NK cells was significantly lower in the FAD group than in the CON group by 0.73-, 0.49-, and 0.70-fold, respectively, indicating that B-lymphocytes are more sensitive to folate deficiency than the other lymphocyte subsets. As expected, the number of neutrophils and eosinophils was significantly lower in the FAD group than in the CON group. However, the number of basophils, the least common type of granulocyte, showed transiently an increasing tendency in the FAD group as compared with the CON group.

Conclusion

These results suggest that folate deficiency induces lymphocytopenia and granulocytopenia in a cell-specific manner.
Literatur
1.
Zurück zum Zitat Krishnaswamy K, Madhavan Nair K. Importance of folate in human nutrition. Br J Nutr. 2001;85:S115–24.PubMedCrossRef Krishnaswamy K, Madhavan Nair K. Importance of folate in human nutrition. Br J Nutr. 2001;85:S115–24.PubMedCrossRef
3.
4.
Zurück zum Zitat Allen LH. Causes of vitamin B12 and folate deficiency. Food Nutr Bull. 2008;29:S20–37.PubMed Allen LH. Causes of vitamin B12 and folate deficiency. Food Nutr Bull. 2008;29:S20–37.PubMed
5.
Zurück zum Zitat Antony AC. In utero physiology: role of folic acid in nutrient delivery and fetal development. Am J Clin Nutr. 2007;85:598S–603S.PubMed Antony AC. In utero physiology: role of folic acid in nutrient delivery and fetal development. Am J Clin Nutr. 2007;85:598S–603S.PubMed
6.
Zurück zum Zitat Metz J. A high prevalence of biochemical evidence of vitamin B12 or folate deficiency does not translate into a comparable prevalence of anemia. Food Nutr Bull. 2008;29:S74–85.PubMed Metz J. A high prevalence of biochemical evidence of vitamin B12 or folate deficiency does not translate into a comparable prevalence of anemia. Food Nutr Bull. 2008;29:S74–85.PubMed
7.
Zurück zum Zitat Liu YK. Effects of alcohol on granulocytes and lymphocytes. Semin Hematol. 1980;17:130–6.PubMed Liu YK. Effects of alcohol on granulocytes and lymphocytes. Semin Hematol. 1980;17:130–6.PubMed
8.
Zurück zum Zitat Koury MJ, Horne DW. Apoptosis mediates and thymidine prevents erythroblast destruction in folate deficiency anemia. Proc Natl Acad Sci USA. 1994;91:4067–71.PubMedCrossRef Koury MJ, Horne DW. Apoptosis mediates and thymidine prevents erythroblast destruction in folate deficiency anemia. Proc Natl Acad Sci USA. 1994;91:4067–71.PubMedCrossRef
9.
Zurück zum Zitat Duthie SJ, Hawdon A. DNA instability (strand breakage, uracil misincorporation, and defective repair) is increased by folic acid depletion in human lymphocytes in vitro. FASEB J. 1998;12:1491–7.PubMed Duthie SJ, Hawdon A. DNA instability (strand breakage, uracil misincorporation, and defective repair) is increased by folic acid depletion in human lymphocytes in vitro. FASEB J. 1998;12:1491–7.PubMed
10.
Zurück zum Zitat De Boer RJ, Mohri H, Ho DD, Perelson AS. Turnover rates of B cells, T cells, and NK cells in simian immunodeficiency virus-infected and uninfected rhesus macaques. J Immunol. 2003;170:2479–87.PubMed De Boer RJ, Mohri H, Ho DD, Perelson AS. Turnover rates of B cells, T cells, and NK cells in simian immunodeficiency virus-infected and uninfected rhesus macaques. J Immunol. 2003;170:2479–87.PubMed
11.
Zurück zum Zitat Thuesen BH, Husemoen LL, Ovesen L, Jørgensen T, Fenger M, Gilderson G, et al. Atopy, asthma, and lung function in relation to folate and vitamin B12 in adults. Allergy. 2010;65:1446–54.PubMedCrossRef Thuesen BH, Husemoen LL, Ovesen L, Jørgensen T, Fenger M, Gilderson G, et al. Atopy, asthma, and lung function in relation to folate and vitamin B12 in adults. Allergy. 2010;65:1446–54.PubMedCrossRef
12.
Zurück zum Zitat Engler H, Dawils L, Hoves S, Kurth S, Stevenson JR, Schauenstein K, et al. Effects of social stress on blood leukocyte distribution: the role of α- and β-adrenergic mechanisms. J Neuroimmunol. 2004;156:153–62.PubMedCrossRef Engler H, Dawils L, Hoves S, Kurth S, Stevenson JR, Schauenstein K, et al. Effects of social stress on blood leukocyte distribution: the role of α- and β-adrenergic mechanisms. J Neuroimmunol. 2004;156:153–62.PubMedCrossRef
13.
Zurück zum Zitat Shirato K, Motohashi N, Tanihata J, Tachiyashiki K, Tomoda A, Imaizumi K. Effects of two types of inactivity on the number of white blood cells in rats. Eur J Appl Physiol. 2006;98:590–600.PubMedCrossRef Shirato K, Motohashi N, Tanihata J, Tachiyashiki K, Tomoda A, Imaizumi K. Effects of two types of inactivity on the number of white blood cells in rats. Eur J Appl Physiol. 2006;98:590–600.PubMedCrossRef
14.
Zurück zum Zitat Shirato K, Tanihata J, Motohashi N, Tachiyashiki K, Tomoda A, Imaizumi K. β2-agonist clenbuterol induced changes in the distribution of white blood cells in rats. J Pharmacol Sci. 2007;104:146–52.PubMedCrossRef Shirato K, Tanihata J, Motohashi N, Tachiyashiki K, Tomoda A, Imaizumi K. β2-agonist clenbuterol induced changes in the distribution of white blood cells in rats. J Pharmacol Sci. 2007;104:146–52.PubMedCrossRef
15.
Zurück zum Zitat Higashino-Matsui Y, Shirato K, Suzuki Y, Kawashima Y, Someya Y, Sato S, et al. Age-related effects of fasting on ketone body production during lipolysis in rats. Environ Health Prev Med. 2012;17:157–63.PubMedCrossRef Higashino-Matsui Y, Shirato K, Suzuki Y, Kawashima Y, Someya Y, Sato S, et al. Age-related effects of fasting on ketone body production during lipolysis in rats. Environ Health Prev Med. 2012;17:157–63.PubMedCrossRef
16.
Zurück zum Zitat Someya Y, Tanihata J, Sato S, Kawano F, Shirato K, Sugiyama M, et al. Zinc-deficiency induced changes in the distribution of rat white blood cells. J Nutr Sci Vitaminol. 2009;55:162–9.PubMedCrossRef Someya Y, Tanihata J, Sato S, Kawano F, Shirato K, Sugiyama M, et al. Zinc-deficiency induced changes in the distribution of rat white blood cells. J Nutr Sci Vitaminol. 2009;55:162–9.PubMedCrossRef
17.
Zurück zum Zitat Ubbink JB, Hayward Vermaak WJ, Bissbort S. Rapid high-performance liquid chromatographic assay for total homocysteine levels in human serum. J Chromatogr. 1991;565:441–6.PubMedCrossRef Ubbink JB, Hayward Vermaak WJ, Bissbort S. Rapid high-performance liquid chromatographic assay for total homocysteine levels in human serum. J Chromatogr. 1991;565:441–6.PubMedCrossRef
18.
Zurück zum Zitat Rogers EJ, Chen S, Chan A. Folate deficiency and plasma homocysteine during increased oxidative stress. N Engl J Med. 2007;357:421–2.PubMedCrossRef Rogers EJ, Chen S, Chan A. Folate deficiency and plasma homocysteine during increased oxidative stress. N Engl J Med. 2007;357:421–2.PubMedCrossRef
19.
Zurück zum Zitat Cacciapuoti F. Hyper-homocysteinemia: a novel risk factor or a powerful marker for cardiovascular diseases? Pathogenetic and therapeutical uncertainties. J Thromb Thrombolysis. 2011;32:82–8.PubMedCrossRef Cacciapuoti F. Hyper-homocysteinemia: a novel risk factor or a powerful marker for cardiovascular diseases? Pathogenetic and therapeutical uncertainties. J Thromb Thrombolysis. 2011;32:82–8.PubMedCrossRef
20.
Zurück zum Zitat Dhur A, Galán P, Christides JP, Polier de Courcy G, Preziosi P, Hercberg S. Effect of folic acid deficiency upon lymphocyte subsets from lymphoid organs in mice. Comp Biochem Physiol Comp Physiol. 1991;98:235–40.CrossRef Dhur A, Galán P, Christides JP, Polier de Courcy G, Preziosi P, Hercberg S. Effect of folic acid deficiency upon lymphocyte subsets from lymphoid organs in mice. Comp Biochem Physiol Comp Physiol. 1991;98:235–40.CrossRef
21.
Zurück zum Zitat Courtemanche C, Elson-Schwab I, Mashiyama ST, Kerry N, Ames BN. Folate deficiency inhibits the proliferation of primary human CD8+ T lymphocytes in vitro. J Immunol. 2004;173:3186–92.PubMed Courtemanche C, Elson-Schwab I, Mashiyama ST, Kerry N, Ames BN. Folate deficiency inhibits the proliferation of primary human CD8+ T lymphocytes in vitro. J Immunol. 2004;173:3186–92.PubMed
22.
Zurück zum Zitat Lin HL, Chen CJ, Tsai WC, Yen JH, Liu HW. In vitro folate deficiency induces apoptosis by a p53, Fas (Apo-1, CD95) independent, bcl-2 related mechanism in phytohaemagglutinin-stimulated human peripheral blood lymphocytes. Br J Nutr. 2006;95:870–8.PubMedCrossRef Lin HL, Chen CJ, Tsai WC, Yen JH, Liu HW. In vitro folate deficiency induces apoptosis by a p53, Fas (Apo-1, CD95) independent, bcl-2 related mechanism in phytohaemagglutinin-stimulated human peripheral blood lymphocytes. Br J Nutr. 2006;95:870–8.PubMedCrossRef
23.
Zurück zum Zitat Kim YI, Hayek M, Mason JB, Meydani SN. Severe folate deficiency impairs natural killer cell-mediated cytotoxicity in rats. J Nutr. 2002;132:1361–7.PubMed Kim YI, Hayek M, Mason JB, Meydani SN. Severe folate deficiency impairs natural killer cell-mediated cytotoxicity in rats. J Nutr. 2002;132:1361–7.PubMed
24.
Zurück zum Zitat Kaplan SS, Basford RE. Effect of vitamin B12 and folic acid deficiencies on neutrophil function. Blood. 1976;47:801–5.PubMed Kaplan SS, Basford RE. Effect of vitamin B12 and folic acid deficiencies on neutrophil function. Blood. 1976;47:801–5.PubMed
Metadaten
Titel
Folate-deficiency induced cell-specific changes in the distribution of lymphocytes and granulocytes in rats
verfasst von
Ikumi Abe
Ken Shirato
Yoko Hashizume
Ryosuke Mitsuhashi
Ayumu Kobayashi
Chikako Shiono
Shogo Sato
Kaoru Tachiyashiki
Kazuhiko Imaizumi
Publikationsdatum
01.01.2013
Verlag
Springer Japan
Erschienen in
Environmental Health and Preventive Medicine / Ausgabe 1/2013
Print ISSN: 1342-078X
Elektronische ISSN: 1347-4715
DOI
https://doi.org/10.1007/s12199-012-0286-6

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