Neutrophil granulocyte functional status and expression of apoptosis markers in children with type 1 diabetes
https://doi.org/10.14341/DM2014377-82
Abstract
In recent years, polymorphonuclear leukocytes have been proven to play an important role in the development of diabetes mellitus (DM). Neutrophil dysfunction contributes to pancreatic tissue damage as well as an increased susceptibility to infection in type 1 DM (T1DM) patients.
Objective.
The objective of this study was to investigate the functional activity of neutrophil granulocytes (NGs) in children with T1DM.
Materials and Methods.
This study involved 25 children aged 7?15 years. To evaluate programmed cell death, the number of NGs expressing apoptosis markers (CD95, CD95L and BCL2) was determined. The functional activity of NGs was determined in terms of phagocytosis and the levels of myeloperoxidase, lysosomal cationic proteins and active oxygen radicals.
Results.
A reduction in the bactericidal activity of NGs with deficiencies in phagocytosis, secretion of active oxygen radicals and functional reserve was found. An increase in the apoptotic potential of NGs was demonstrated, which was accompanied by an increase in CD95 expression and a decrease in BCL2 expression. An increase in the cytotoxic potential of neutrophils in the form of enhanced levels of myeloperoxidase and lysosomal cationic proteins was revealed.
Conclusions.
Therefore, an increase in the apoptotic potential of NGs associated with functional and metabolic changes may reflect the active involvement of NGs in the immunopathogenesis of T1DM.
Objective.
The objective of this study was to investigate the functional activity of neutrophil granulocytes (NGs) in children with T1DM.
Materials and Methods.
This study involved 25 children aged 7?15 years. To evaluate programmed cell death, the number of NGs expressing apoptosis markers (CD95, CD95L and BCL2) was determined. The functional activity of NGs was determined in terms of phagocytosis and the levels of myeloperoxidase, lysosomal cationic proteins and active oxygen radicals.
Results.
A reduction in the bactericidal activity of NGs with deficiencies in phagocytosis, secretion of active oxygen radicals and functional reserve was found. An increase in the apoptotic potential of NGs was demonstrated, which was accompanied by an increase in CD95 expression and a decrease in BCL2 expression. An increase in the cytotoxic potential of neutrophils in the form of enhanced levels of myeloperoxidase and lysosomal cationic proteins was revealed.
Conclusions.
Therefore, an increase in the apoptotic potential of NGs associated with functional and metabolic changes may reflect the active involvement of NGs in the immunopathogenesis of T1DM.
About the Authors
Lyudmila Yur'evna Barycheva
Stavropol State Medical University, Stavropol
Russian Federation
MD, PhD, Professor of the Chair of Pediatric Infectious Diseases
Competing Interests:
Russian Federation
MD, PhD, Professor of the Chair of Pediatric Infectious Diseases
Competing Interests:
Работа выполнена в рамках федеральной целевой научной программы. Номер государственной регистрации 01200954364.
Выполнение настоящего исследования одобрено Локальным Этическим комитетом ГБОУ ВПО «Ставропольский государственный медицинский университет» Министерства здравоохранения РФ (ул. Мира, 310). Протокол N16 от 14 мая 2012 г.
Конфликт интересов, связанных с рукописью отсутствует.
Natalya Eduardovna Erdni-Goryaeva
Stavropol State Medical University, Stavropol
Russian Federation
MD, Endocrinologist of the Stavropol Regional Clinical Diagnostic Center; Competitor of the Chair of Pediatric Infectious Diseases
Russian Federation
MD, Endocrinologist of the Stavropol Regional Clinical Diagnostic Center; Competitor of the Chair of Pediatric Infectious Diseases
Galina Alekseevna Alexandrovich
Stavropol State Medical University, Stavropol
Russian Federation
MD, PhD, Associate Professor, Honored Doctor of Russia, Head of the Chair of Endocrinology, Pediatric Endocrinology, and Diabetology
Russian Federation
MD, PhD, Associate Professor, Honored Doctor of Russia, Head of the Chair of Endocrinology, Pediatric Endocrinology, and Diabetology
References
1. Alba-Loureiro TC, Hirabara SM, Mendonça JR, Curi R, Pithon-Curi TC. Diabetes causes marked changes in function and metabolism of rat neutrophils. Journal of Endocrinology 2006;188(2):295-303. doi: 10.1677/joe.1.06438
2. Alba-Loureiro TC, Munhoz CD, Martins JO, Cerchiaro GA, Scavone C, Curi R, et al. Neutrophil function and metabolism in individuals with diabetes mellitus. Braz J Med Biol Res 2007;40(8):1037-1044. doi: 10.1590/S0100-879X2006005000143
3. Valle A, Giamporcaro GM, Scavini M, Stabilini A, Grogan P, Bianconi E, et al. Reduction of Circulating Neutrophils Precedes and Accompanies Type 1 Diabetes. Diabetes 2013;62(6):2072-2077. doi: 10.2337/db12-1345
4. Tong PC, Lee KF, So WY, Ng MH, Chan WB, Lo MK, et al. White Blood Cell Count Is Associated With Macro- and Microvascular Complications in Chinese Patients With Type 2 Diabetes. Diabetes Care 2004;27(1):216-222. doi: 10.2337/diacare.27.1.216
5. Lo H, Lin S, Wang Y. The relationship among serum cytokines, chemokine, nitric oxide, and leptin in children with type 1 diabetes mellitus. Clinical Biochemistry 2004;37(8):666-672. doi: 10.1016/j.clinbiochem.2004.02.002
6. Karima M, Kantarci A, Ohira T, Hasturk H, Jones VL, Nam B, et al. Enhanced superoxide release and elevated protein kinase C activity in neutrophils from diabetic patients: association with periodontitis. Journal of Leukocyte Biology 2005;78(4):862-870. doi: 10.1189/jlb.1004583
7. Балаболкин МИ, Клебанова ЕА, Креминская ВМ. Патогенез ангиопатий при сахарном диабете. Сахарный диабет. 1999;(1):2-8. [Balabolkin MI, Klebanova EM, Kreminskaya VM. Patogenez angiopatiy pri sakharnom diabete. Diabetes mellitus. 1999;(1):2-8. doi: 10.14341/2072-0351-5725]
8. Hayasaka S, Zhang X, Cui H, Yanagisawa S, Chi Z, Hayasaka Y, et al. Chemokines and Sho (Zheng in Chinese) of Chinese-Korean-Japanese medicine in patients with diabetic vitreoretinopathy. Am. J. Chin. Med. 2006;34(04):537-543. doi: 10.1142/S0192415X06004077
9. Morii T, Fujita H, Narita T, Shimotomai T, Fujishima H, Yoshioka N, et al. Association of monocyte chemoattractant protein-1 with renal tubular damage in diabetic nephropathy. J. Diabetes Complications 2003;17(1):11-15. doi: 10.1016/S1056-8727(02)00176-9
10. Nabi AHMN, Islam LN, Rahman MM, Biswas KB. Polymorphonuclear Neutrophil Dysfunctions Streptozotocin-induced Type 1 Diabetic Rats. Journal of Biochemistry and Molecular Biology 2005;38(6):661-667. PubMed PMID: 16336780
11. Kannan Y, Tokunaga M, Moriyama M, Kinoshita H, Nakamura Y. Diabetic neutrophil dysfunction and troglitazone. Clin Exp Immunol 2004;137(2):263-271. doi: 10.1111/j.1365-2249.2004.02532.x
12. Chanchamroen S, Kewcharoenwong C, Susaengrat W, Ato M, Lertmemongkolchai G. Human polymorphonuclear neutrophil responses to Burkholderia pseudomallei in healthy and diabetic subjects. Infect Immun 2008;77(1):456-463. doi: 10.1128/IAI.00503-08
13. Tennenberg SD. Absence of Lipopolysaccharide-Induced Inhibition of Neutrophil Apoptosis in Patients With Diabetes. Arch Surg 1999;134(11):1229-1233. doi: 10.1001/archsurg.134.11.1229
14. Casqueiro J, Casqueiro J, Alves C. Cresio Infections in patients with diabetes mellitus: A review of pathogenesis. Indian J Endocrinol Metab 2012;16 Suppl 1(l1):27. doi: 10.4103/2230-8210.94253
15. Walrand S, Guillet C, Boirie Y, Vasson M. In vivo evidences that insulin egulates human polymorphonuclear neutrophil functions. Journal of Leukocyte Biology 2004;76(6):1104-1110. doi: 10.1189/jlb.0104050
16. Kaczmarek M, Lewandowicz-Uszyńska A, Iwanicka Z, Jankowski A. Whole blood neutrophil chemiluminescence in children with diabetes depending on their clinical condition. Centr Eur J Immunol 2012;4(4):345-349. doi: 10.5114/ceji.2012.32723
17. Ziegler D, Sohr CG, Nourooz-Zadeh J. Oxidative stress and antioxidant defense in relation to the severity of diabetic poly-neuropathy and autonomic neuropathy. Diabetes Care 2004;27(9):2178-2183. doi: 10.2337/diacare.27.9.2178
18. Seo KH, Na JO, Moon SH, Uh ST, Kim YH, Park CS. Neutrophil Apoptosis and H2O2 Release by LPS in Diabetics. Tuberculosis and Respiratory Diseases. 2004; 57 (3): 250-256. Available from: http://www.e-trd.org/abstract/view_article.php?year=2008&no=707&page_list=abslist
19. Zhang B, Hirahashi J, Cullere X, Mayadas TN. Elucidation of Molecular Events Leading to Neutrophil Apoptosis following Phagocytosis: cross-talk between caspase 8, reactive oxygen species, and mapk/erk activation. Journal of Biological Chemistry 2003;278(31):28443-28454. doi: 10.1074/jbc.M210727200
20. Glowacka E, Banasik M, Lewkowicz P, Tchorzewski H. The effect of LPS on neutrophils from patients with high risk of type 1 diabetes mellitus in relation to IL-8, IL-10 and IL-12 production and apoptosis in vitro. Scand J Immunol 2002;55(2):210-217. doi: 10.1046/j.1365-3083.2002.01046.x
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For citations:
Barycheva L.Yu., Erdni-Goryaeva N.E., Alexandrovich G.A. Neutrophil granulocyte functional status and expression of apoptosis markers in children with type 1 diabetes. Diabetes mellitus. 2014;17(3):77-82. https://doi.org/10.14341/DM2014377-82
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