Differences in age modulates neutrophils function

DOI: 10.4236/abc.2014.41008   PDF   HTML   XML   3,896 Downloads   5,576 Views   Citations


The sexual maturation in all mammals is the period in which the quiescent gonads are activated by gonadotropins from anterior pituitary, increasing the secretion of sexual hormones. Sexual maturation it is also related with the development of several other body features such as body mass and maturation of the circulatory, skeletal and hematopoietic systems. The aim of the present study was to evaluate the function of neutrophils submitted to in vivo lower and higher concentration of testosterone (sexually immature: 60 days and sexually mature: 90 days). Using different approaches we evaluated cell viability and function and gene expression in rat neutrophils from 60 and 90 days-old animals. Neutrophils from 90 days-old rats showed a decrease in phagocytic and fungicidal capacity, without change in cellular viability. Additionally, we verified that sexual maturation induced increase in production of reactive oxygen and nitrogen species (RONS) and also in TNF-α, IL-6 and IL-10 cytokines. In conclusion, our data suggest that increase in testosterone levels induced significant alteration in neutrophil function, impairing phagocytic capacity.

Share and Cite:

Lagranha, C. , Alba-Loureiro, T. , da Silva, A. , de Lima, D. , Pedroza, A. , Ferreira, D. and Pithon-Curi, T. (2014) Differences in age modulates neutrophils function. Advances in Biological Chemistry, 4, 51-58. doi: 10.4236/abc.2014.41008.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Bogin, E., Marom, M. and Levi, Y. (1994) Changes in serum, liver and kidneys of cisplatin-treated rats; effects of antioxidants. European Journal of Clinical Chemistry and Clinical Biochemistry, 32, 843-851.
[2] Amiel, S.A., et al. (1991) Insulin resistance of puberty: A defect restricted to peripheral glucose metabolism. The Journal of Clinical Endocrinology and Metabolism, 72, 277-282.
[3] Kiess, W., et al. (1995) Salivary cortisol levels throughout childhood and adolescence: Relation with age, pubertal stage, and weight. Pediatric Research, 37, 502-506.
[4] Liker, H.R., et al. (1988) Blood pressure and body size in precocious puberty. Acta paediatrica Scandinavica, 77, 294-298. http://dx.doi.org/10.1203/00006450-199504000-00020
[5] Weaver, C.M., et al. (1996) Calcium retention estimated from indicators of skeletal status in adolescent girls and young women. The American Journal of Clinical Nutrition, 64, 67-70.
[6] Grumbach, M.M. and Styne, D.M. (1998) Puberty: Ontogeny, Neuroendocrinology, physiology and disorders. In: Willians Textbook of Endocrinol, 9th Edition, 1509-1625.
[7] Chao, T.C., Van Alten, P.J. and Walter, R.J. (1994) Steroid sex hormones and macrophage function: Modulation of reactive oxygen intermediates and nitrite release. American Journal of Reproductive Immunology, 32, 43-52.
[8] McMurray, R.W., et al. (2001) Differential effects of sex steroids on T and B cells: Modulation of cell cycle phase distribution, apoptosis and bcl-2 protein levels. Pathobiology, 69, 44-58.
[9] Giron-Gonzalez, J.A., et al. (2000) Consistent production of a higher TH1:TH2 cytokine ratio by stimulated T cells in men compared with women. European Journal of Endocrinology, 143, 31-36.
[10] Bouman, A., et al. (2004) Gender difference in the non-specific and specific immune response in humans. American Journal of Reproductive Immunology, 52, 19-26.
[11] Posma, E., et al. (2004) The effect of testosterone on cytokine production in the specific and non-specific immune response. American Journal of Reproductive Immunology, 52, 237-243.
[12] Janele, D., et al. (2006) Effects of testosterone, 17beta-estradiol, and downstream estrogens on cytokine secretion from human leukocytes in the presence and absence of cortisol. Annals of the New York Academy of Sciences, 1069, 168-182. http://dx.doi.org/10.1196/annals.1351.015
[13] Zanato, V.F., et al. (1994) Sexual development of male Wistar rats. Brazilian Journal of Medical and Biological Research, 27, 1273-1280.
[14] Pithon-Curi, T.C., et al. (2003) Glutamine delays spontaneous apoptosis in neutrophils. American Journal of Physiology-Cell Physiology, 284, C1355-C1361.
[15] Lagranha, C.J., et al. (2005) The effect of glutamine supplementation on the function of neutrophils from exercised rats. Cell Biochemistry and Function, 23, 101-107.
[16] Lagranha, C.J., et al. (2007) Glutamine supplementation prevents exercise-induced neutrophil apoptosis and reduces p38 MAPK and JNK phosphorylation and p53 and caspase 3 expression. Cell Biochemistry and Function, 25, 563-569.
[17] Lagranha, C.J., et al. (2004) Beneficial effect of glutamine on exercise-induced apoptosis of rat neutrophils. Medicine & Science in Sports & Exercise, 36, 210-217.
[18] Lagranha, C.J., et al. (2008) Neutrophil fatty acid composition: Effect of a single session of exercise and glutamine supplementation. Amino Acids, 35, 243-245.
[19] Levada-Pires, A.C., et al. (2008) Neutrophil death induced by a triathlon competition in elite athletes. Medicine & Science in Sports & Exercise, 40, 1447-1454.
[20] Levada-Pires, A.C., et al. (2010) The effect of an adventure race on lymphocyte and neutrophil death. European Journal of Applied Physiology, 109, 447-453.
[21] Nicoletti, I., et al. (1991) A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. Journal of Immunological Methods, 139, 271-279.
[22] Alba-Loureiro, T.C., et al. (2006) Diabetes causes marked changes in function and metabolism of rat neutrophils. Journal of Endocrinology, 188, 295-303.
[23] Sasada, M. and Johnston Jr., R.B. (1980) Macrophage microbicidal activity. Correlation between phagocytosis-associated oxidative metabolism and the killing of Candida by macrophages. The Journal of Experimental Medicine, 152, 85-98.
[24] Sasada, M. et al. (1987) Candidacidal activity of monocyte-derived human macrophages: Relationship between Candida killing and oxygen radical generation by human macrophages. Journal Leukocyte Biology, 41, 289-294.
[25] Stevens, P. and Hong, D. (1985) The role of myelope-roxidase and superoxide anion in the luminol- and lucigenin-dependent chemiluminescence of human neutrophils. Microchemical Journal, 30, 11.
[26] Pick, E. and Mizel, D. (1981) Rapid microassays for the measurement of superoxide and hydrogen peroxide production by macrophages in culture using an automatic enzyme immunoassay reader. Journal of Immunological Methods, 46, 211-226.
[27] Ding, Y., Ma, K. and Tsui, Z.C. (1998) Induction of nitric oxide production by ganglioside GM3 in murine peritoneal macrophages activated for tumor cytotoxicity. In Vivo, 12, 357-361.
[28] de Lima, T.M., et al. (2006) Fatty acid control of nitric oxide production by macrophages. FEBS Letters, 580, 3287-3295. http://dx.doi.org/10.1016/j.febslet.2006.04.091
[29] Alba-Loureiro, T.C., Pithon-Curi, T.C. and Curi, R. (2008) Reduced cytokine production by glycogen-elicited peritoneal cells from diabetic rats. Shock, 30, 308-310.
[30] Chomczynski, P. and Sacchi, N. (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extration. Analytical Biochemistry, 162, 156-159.
[31] Chomczynski, P. (1993) A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques, 15, 532-534.
[32] Levada-Pires, A.C., et al. (2007) Exercise training raises expression of the cytosolic components of NADPH oxidase in rat neutrophils. European Journal of Applied Physiology, 100, 153-160.
[33] Higuchi, M. (1992) Reduced nicotinamide adenine dinucleotide oxidase involvement in defense against oxygen toxicity of Streptococcus mutans. Oral Microbiology and Immunology, 7, 309-314.
[34] Livak, K.J. and Schmittgen, T.D. (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25, 402-408.
[35] Pfaffl, M.W. (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Research, 29, e45.
[36] Zhang, X., Ding, L. and Sandford, A.J. (2005) Selection of reference genes for gene expression studies in human neutrophils by real-time PCR. BMC Molecular Biology, 6, 4. http://dx.doi.org/10.1186/1471-2199-6-4
[37] Olinescu, R., et al. (1994) Steroid hormones may modulate the chemiluminescence emission produced by poly-morphonuclear leukocytes. Romanian Journal of Internal Medicine, 32, 37-46.
[38] al-Afaleq, A.I. and Homeida, A.M. (1998) Effects of low doses of oestradiol, testosterone and dihydrotestosterone on the immune response of broiler chicks. Immunopharmacology and Immunotoxicology, 20, 315-327.
[39] Marin, D.P., et al. (2010) Testosterone suppresses oxidative stress in human neutrophils. Cell Biochemistry and Function, 28, 394-402.
[40] Bekesi, G., et al. (2001) Plasma concentration of myeloperoxidase enzyme in pre- and post-climacterial people: Related superoxide anion generation. Experimental Gerontology, 37, 137-148.
[41] Sumi, D., et al. (2003) 17beta-estradiol inhibits NADPH oxidase activity through the regulation of p47phox mRNA and protein expression in THP-1 cells. Biochimica et Biophysica Acta, 1640, 113-118.

comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.