Peculiarities of leukocyte apoptosis modulation in children with pyelonephritis
AbstractOne of the leading places among inflammatory diseases of the urinary tract of children belongs to pyelonephritis, the course of which presents in most cases as a severe infectious disease threatening the patient’s life, which is the main reason for development of chronic kidney failure. This study was conducted to compare apoptosis stages in peripheral blood of children of different age categories with pyelonephritis depending on etiological factor and complications. The problem of mechanisms underlying immune system misregulation, especially functional activity of leukocytes in children with pyelonephritis, have not been explored in recent years. Assessment of leukocytes (neutrophils) apoptosis stages in peripheral blood of children of different age categories with pyelonephritis depending on complications and etiological factor was the aim of present study. The children's peripheral blood samples were analysed and assessed using a flow cytofluorimeter. The present study demonstrates an increase of the level of apoptotic cells at an early stage of apoptosis in children of all age categories with chronic pyelonephritis, which can be explained by associations of a wide range of pathogens and the presence of sequelae. An increase in the number of apoptotic cells in the late stage of apoptosis is observed in children aged 1 month – 8 years, in children 8–18 years, the amount of apoptotic cells is reduced by 1.5 times. The study of apoptosis stages allows complete characterization of the dynamics of the apoptotic process and supplementation of the pathogenesis of pyelonephritis in children. Such studies will make it possible to affect apoptosis modulation to regulate or correct it and encourage the finding of innovative solutions in the treatment related to influence on the immune response. We conclude that enhancement of peripheral blood leukocyte apoptosis in chronic form of pyelonephritis especially in young children is due to the polyetiology of this form of pyelonephritis and the development of complications.
Akematsu, T., & Endoh, H. (2010). Role of apoptosis-inducing factor (AIF) in programmed nuclear death during conjugation in Tetrahymena thermophila. BMC Cell Biology, 11, 13.
Anis, S. (2016). Immunologists’ perspective of nephropathology. Journal of Nephropathology, 5(2), 62–64.
Chen, M., Tofighi, R., Bao, W., Aspevall, O., Jahnukainen, T., Gustafsson, L. E., Ceccatelli, S., & Celsi, G. (2005). Carbon monoxide prevents apoptosis induced by uropathogenic Escherichia coli toxins. Pediatric Nephrology, 21(3), 382–389.
Delogu, G., Famularo, G., Tellan, G., Marandola, M., Antonucci, A., Signore, M., Marcellini, S., & Moretti, S. (2008). Lymphocyte apoptosis, caspase activation and inflammatory response in septic shock. Infection, 36(5), 485–487.
Elmore, S. (2007). Apoptosis: A review of programmed cell death. Toxicologic Pathology, 35(4), 495–516.
Greineder, C. F., Nelson, P. W., Dressel, A. L., Erba, H. P., & Younger, J. G. (2007). In vitro and in silico analysis of annexin V binding to lymphocytes as a biomarker in emergency department sepsis studies. Academic Emergency Medicine, 14(9), 763–771.
Hennessy, E. J., Parker, A. E., & O’Neill, L. A. J. (2010). Targeting toll-like receptors: Emerging therapeutics? Nature Reviews Drug Discovery, 9(4), 293–307.
Hermiston, M. L., Xu, Z., & Weiss, A. (2003). CD45: A critical regulator of signaling thresholds in immune cells. Annual Review of Immunology, 21(1), 107–137.
Hodyreva, L. A., Sinyuhin, V. N., & Harlamova, L. A. (2010). Osobennosti induktsii apoptoza v culture limfotsitov perifericheskoy krovi bolnyih s razlichnyimi formami ostrogo pielonefrita [Features of apoptosis induction in peripheral blood lymphocytes culture in patients with various forms of acute pyelonephritis]. Eksperimentalnaya i Klinicheskaya Urologiya, 2, 2–10 (in Russian).
Holmstrom, T. H., & Eriksson, J. E. (2000). Phosphorylation-based signaling in fas receptor-mediated apoptosis. Critical Reviews in Immunology, 20(2), 121–152.
Joshi, S., Wang, W., Peck, A. B., & Khan, S. R. (2015). Activation of the NLRP3 inflammasome in association with calcium oxalate crystal induced reactive oxygen species in kidneys. Journal of Urology, 193(5), 1684–1691.
Joza, N., Susin, S., Daugas, E., Stanford, W. L., Cho, S. K., Li, C. Y., Sasaki, T., Elia, A. J., Cheng, H.-Y. M., Ravagnan, L., Ferri, K. F., Zamzami, N., Wakeham, A., Hakem, R., Yoshida, H., Kong, Y.-Y., Mak, T. W., Zúñiga-Pflücker, J. C., Kroemer, G., & Penninger, J. M. (2001). Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death. Nature, 410, 549–554.
Kammili, N., Maheswari, U., Palvai, S., & Anuradha, P. (2013). Hemagglutination and biofilm formation as virulence markers of uropathogenic Escherichia coli in acute urinary tract infections and urolithiasis. Indian Journal of Urology, 29(4), 277.
Keel, M., Mica, L., Stover, J., Stocker, R., Trentz, O., & Härter, L. (2005). Thiopental-induced apoptosis in lymphocytes is independent of CD95 activation. Anesthesiology, 103(3), 576–584.
Kumagai, N., Inoue, C. N., Kondo, Y., & Iinuma, K. (2000). Mitogenic action of lysophosphatidic acid in proximal tubular epithelial cells obtained from voided human urine. Clinical Science, 99, 561–567.
Lee, K.-Y. (2016). New insights for febrile urinary tract infection (acute pyelonephritis) in children. Childhood Kidney Diseases, 20(2), 37–44.
Mattsby-Baltzer, I., Hanson, L. A., Kaijser, B., Larsson, P., Olling, S., & Svanborg-Eden, C. (2012). Experimental Escherichia coli ascending pyelonephritis in rats: Changes in bacterial properties and the immune response to surface antigens. Infection and Immunity, 35, 639–646.
Meier, P., Dayer, E., Blanc, E., & Wauters, J. P. (2002). Early T-cell activation correlates with expression of apoptosis markers in patients with end stage renal disease. Journal of the American Society of Nephrology, 13(1), 204–212.
National Kidney Foundation (2002). K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification and stratification. American Journal of Kidney Diseases, 39, 1–266.
Oktem, G., Altay, B., Turna, B., Aktug, H., Yavasoglu, A., Yilmaz, O., & Semerci, B. (2009). Determination of nitric oxide synthase activity and apoptosis of germ cells in different obstruction models. Acta Histochemica, 111(2), 119–126.
Olson, P., & Hunstad, D. (2016). Subversion of host innate immunity by uropathogenic Escherichia coli. Pathogens, 5(1), 2–12.
Ostapchenko, L. I., Synelnyk, T. B., Rybalchenko, T. V., & Rybalchenko, V. K. (2010). Biokhimichni mekhanizmy apoptozu [Biochemical mechanisms of apoptosis]. Kyivskyi Universytet, Kyiv (in Ukrainian).
Rheinländer, A., Schraven, B., & Bommhardt, U. (2018). CD45 in human physiology and clinical medicine. Immunology Letters, 196, 22–32.
Roger, P.-M., Hyvernat, H., Breittmayer, J.-P., Dunais, B., Dellamonica, J., Bernardin, G., & Bernard, A. (2009). Enhanced T-cell apoptosis in human septic shock is associated with alteration of the costimulatory pathway. European Journal of Clinical Microbiology and Infectious Diseases, 28(6), 575–584.
Saad, K., Elsayh, K. I., Zahran, A. M., & Sobhy, K. M. (2014). Lymphocyte populations and apoptosis of peripheral blood B and T lymphocytes in children with end stage renal disease. Renal Failure, 36(4), 502–507.
Serlachius, E., Sundelin, B., Eklöf, A.-C., Jahnke, M., Laestadius, A., & Aperia, A. (1997). Pyelonephritis provokes growth retardation and apoptosis in infant rat renal cortex. Kidney International, 51(6), 1855–1862.
Spencer, J. D., Schwaderer, A. L., Becknell, B., Watson, J., & Hains, D. S. (2013). The innate immune response during urinary tract infection and pyelonephritis. Pediatric Nephrology, 29(7), 1139–1149.
Sung, S. H., Woo, S., & Lee, S. J. (2000). Correlation between renal growth retardation and apoptosis of cortical tubules in experimentally induced acute ascending pyelonephritis in infant rat. The Korean Journal of Pathology, 34(12), 1001–1008.
Teixeira, D., Longo-Maugeri, I., Duarte, Y., Lebrao, M., & Bueno, V. (2013). Evaluation of renal function and immune system cells in elderly individuals from São Paulo City. Clinics, 68(1), 39–44.
Tittel, A. P., Heuser, C., Ohliger, C., Knolle, P. A., Engel, D. R., & Kurts, C. (2011). Kidney dendritic cells induce innate immunity against bacterial pyelonephritis. Journal of the American Society of Nephrology, 22(8), 1435–1441.
Wang, H., Jiang, X. M., Xu, J. H., Xu, J., Tong, J. X., & Wang, Y. W. (2008). The profile of gene expression and role of nuclear factor kappa B on glomerular injury in rats with Thy-1 nephritis. Clinical and Experimental Immunology, 152(3), 559–567.
Whiteside, S. A., Razvi, H., Dave, S., Reid, G., & Burton, J. P. (2015). The microbiome of the urinary tract – a role beyond infection. Nature Reviews Urology, 12(2), 81–90.
Zhang, G., Oldroyd, S. D., Huang, L. H., Yang, B., Li, Y., Ye, R., & ElNahas, A. M. (2001). Role of apoptosis and Bcl-2/Bax in the development of tubulointerstitial fibrosis during experimental obstructive nephropathy. Experimental Nephrology, 9(2), 71–80.
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons «Attribution» 4.0 License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.