Українська Русский English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2012; 58(3): 9-18

Hematopoietic stem cells and immune status of subjects with different hypoxic tolerance

T.V. Serebrovskaya, I.S. Nikolsky, L.I. Taranukha, V.V. Nikolska, S.M. Galytska, V.A. Ishchuk

  1. O.O.Bogomoletz Institute of Physiology, National Academyof Sciences of Ukraine, Kyiv, Ukraine;
  2. Institute of Genetic and Regenerative Medicine, Academy of Medical Sciences, Kyiv, Ukraine;
  3. State Institute of Gerontology, Academy of MedicalSciences, Kyiv, Ukraine.


Intermittent hypoxia treatment (IHT) is gaining attention as a clinical modality due to its capacity to protect cells, tissues, organs, and the whole organism from more intense and/or sustained hypoxia, ischemia and other stresses, to enhance physical and mental capacity. Circulating hematopoietic stem and progenitor cells (HSPC) play an important role in immune response to hypoxia ensuring tissue reparation processes, formation of all types of blood cells etc. There exist considerable individual differences in the capability to mobilize HSPC. This study was designed to compare the effects of IHT on HSPC, various factors of natural resistance and main humoral and cellular components of adaptive immunity in peripheral blood of subjects with normal and reduced tolerance to hypoxic load. Ten healthy male volunteers (age 30,9±0,6 y.o.) participated in the study and were divided into two groups with reduced (RT, 5 subjects) and normal (NT, 5 subjects) hypoxic tolerance. Criterion for reduced hypoxic tolerance detection was the exceeding deviation of arterial blood pressure, minute ventilation, SаO2 and/or pathological changes in ECG during sustained hypoxia test (breathing with 10% oxygen, 10 min). All subjects were studied before and after a 14 day IHT program consisting of four 5 min bouts/d of breathing 10% O2, with intervening 5 min room air exposures. Immunofuorescence detected HSPCs as CD45+CD34+ cells in peripheral blood. Phagocytic and bactericidal activities of neutrophils, circulating immunoglobulins (IgM, IgG, IgA), immune complexes, complement, and cytokines (EPO, TNF-a, IL-4, IFN-g) were measured. It was shown that NT subjects had higher hemoglobin and erythrocytes level, hematocrit and physical working capacity, but leukocytes, lymphocytes, CD8+-cells contents and level of IgA were lower than in RT. These differences were preserved after IHT course. CD45+34+cells content was the same in both groups before IHT, but RT subjects demonstrated twice decrease in HSPCs content after IHT as opposed to NT who did not show distinct reactions. A decrease in HSPCs is probably associated with the change of their migration capacity. However, it remains unclear whether there is an inhibition of HSPCs migration into circulation or an activation of HSPCs escape from circulation. In both cases tissues could accumulate more HSPCs which in turn could enhance hematopoiesis and general regenerative potential. RT group also had lower complement, induced and reserve bactericidal activities of neutrophils which were signifcantly increased after IHT reaching the level of NT. The level of cytokines EPO, TNF-a and IFN-g did not differ in both groups before IHT but considerably reduced level of IL-4 was registered in RN patients. IHT sharply lowered pro-infammatory cytokine TNF-a in both groups, signifcantly increased IL-4 in RT subjects; increasing behavior of IFN-g was observed in both groups. EPO was not affected considerably during the study. The findings support the potential for eventual application of IHT for immunotherapy, especially for patients with reduced hypoxic tolerance.


  1. Гаркави Л.Х., Квакина В.Б., Кузьменко Т.С. Антистрессорные реакции и активационная терапия. – М.: Имедис, 1998. – 565 с.
  2. Дугласс С.Д., Куи П.Г. Исследование фагоцитоза в клинической практике. – М.: Медицина, 1983. – 193 c.
  3. Коркушко О.В., Серебровська Т.В., Шатило В.Б., Іщук В.О., Лопата В.О. Вибір оптимальних режимів для проведення інтервальних нормабаричних гіпоксич-них тренувань у медичній практиці та спортивній медицині: Метод. рекомендації. – К., 2010. – 30 с.
  4. Маянский А.Н., Маянский Д.Н. Очерки о нейтрофиле и макрофаге. – Новосибирск: Наука, 1983. – 343 c.
  5. Серебровская Т.В. Оценка степени генетической обусловленности реакций кардио-респираторной системы человека на гипоксию и гиперкапнию // Косм. биология и авиакосм. медицина. – 1982. – 16, №6. – С. 54–58.
  6. Ушаков И.Б., Усов В.М., Дворников М.В., Бухтияров И.В. Современные аспекты проблемы гипоксии в тео­рии и практике высотной физиологии и авиационной медицины. – В кн.: Проблемы гипоксии: молекуляр­ные, физиологические и медицинские аспекты. – М.; Воронеж: Истоки, 2004. – С. 170–200.
  7. Cipolleschi M.G., Dello Sbarba P., Olivotto M. The role of hypoxia in the maintenance of hematopoietic stem cells // Blood. – 1993. – 82. – P. 2031–2037.
  8. Ciulla M.M., Giorgetti A., Lazzari L., Cortiana M., Silvestris I., Annoni G., De Asmundis C., Fiore A.V., Montelatici E., Paliotti R., Magrini F., Rebulla P., Cortelezzi A. High-altitude trekking in the Himalayas increases the activity of circulating endothelial cells // Amer. J. Hematol. – 2005. – 79. – P. 76–78.
  9. 9. Cooper K.H. The new aerobics. M. Evans and Company, Inc., 1970. – 192 p.
  10. 10. Danet G.H., Pan Y., Luongo J.L., Bonnet D.A., Simon M.C. Expansion of human SCID-repopulating cells under hypoxic conditions // J. Clin. Invest. – 2003. – 112. – P. 126–135.
  11. Djeu J.Y., Stocks N., Zoon K., Stanton G.J., Timonen T., Herberman R.B. Positive self regulation of cytotoxicity in human natural killer cells by production of interferon upon exposure to infuenza and herpes viruses // J. Exp. Med. – 1982. – 156. – P. 1222–1234.
  12. Gilmour J., Lavender P. Control of IL-4 expression in T helper 1 and 2 cells // Immunology. – 2008. – 124. – P. 437–444.
  13. Haskova V., Kaslik L., Malejerwa M. A new method of the determination of the circulating immune complexes in liquor (in Russian) // Gasopis Lekaru Ceskych. – 1977. 116 (14). – P. 436–437.
  14. Krstic A., Vlaski M., Hammoud M., Chevaleyre J., Duchez P. , Jovcic G., Bugarski D., Milenkovic P., Bourin P., Boiron J.M., Praloran V., Ivanovic Z. Low O2 concentrations enhance the positive effect of IL-17 on the maintenance of erythroid progenitors during co-culture of CD34+ and mesenchymal stem cells // Eur Cytokine Netw. – 2009. – 20. – P. 10–16.
  15. Manchini G., Vaerman J.-P., Carbonera A.O., Heremans J.F. A simple radial-diffusion method for the immunological quantitation of protein. – In: Proceedings of the biological fuids. – Amsterdam, London, N.Y.: Elsevier, 1964. – P. 370–379.
  16. Mancuso P., Peccatori F., Rocca A., Calleri A., Antoniotti P., Rabascio C., Saronni L., Zorzino L., Sandri M.T., Zubani A., Bertolini F. Circulating endothelial cell number and viability are reduced by exposure to high altitude // Endothelium. – 2008. – 15. – P. 53–58.
  17. Nikolsky I., Serebrovska T.V. Role of hypoxia in stem cell development and functioning. Review // Фізіол. журн. – 2009. – 55, № 4. – С. 116–130.
  18. Ojeda-uribe M., Sovalat H., Bourderont D., Brunot A., Marr A., Levwandowski H., Chaboute V., Peter P., Henon P. Peripheral blood and BM CD34+ CD38-cells show better resistance to cryapreservation than CD34+ CD38+ cells in autologous stem cell transplantation // Cytotherapy. – 2004. – 6, № 6. – P.571–583.
  19. 19. Olive P.L., Luo C.M., Banath J.P. Local hypoxia is produced at sites of intratumour injection // Brit. J. Cancer. – 2002. – 86. – P. 429–435.
  20. 20. Serebrovska T., Nikolsky I., Ishchuk V. Human adaptation to intermittent hypoxia: effects on hematopoietic stem cells and immune function. – In: Adaptation Biology and Medicine, Vol. 6: Cell Adaptations and Challenges, Eds: P.Wang, C.-H. Kuo, N.Takeda and P.K.Singal, Canada: Narosa Publisher. – 2010. – P. 181–191.
  21. Tang Y.L., Zhu W., Cheng M., Chen L., Zhang J., Sun T., Kishore R., Phillips M.I., Losordo D.W., Qin G. Hypoxic preconditioning enhances the beneft of cardiac progenitor cell therapy for treatment of myocardial infarction by inducing CXCR4 expression // Circulat. Res. – 2009. – 104. – P. 1209–1216.
  22. Theiss H.D., Adam M., Greie S., Schobersberger W., Humpeler E., Franz W.M. Increased levels of circulating progenitor cells after 1-week sojourn at moderate altitude (Austrian Moderate Altitude Study II, AMAS II) // Respirat Physiol Neurobiol. – 2008. – 160. – P. 232–238.
  23. Viscor G., Javierre C., Pages T., Ventura J.L., Ricart A., Martin-Henao G., Azqueta C., Segura R. Combined intermittent hypoxia and surface muscle electrostimu-lation as a method to increase peripheral blood progenitor cell concentration // J. Transl Med. – 2009. – 7. – P. 91.
  24. Wang J.S., Lin H.Y., Cheng M.L., Wong M.K. Chronic intermittent hypoxia modulates eosinophil- and neutrophil-platelet aggregation and inflammatory cytokine secretion caused by strenuous exercise in men // J. Appl. Physiol. – 2007. – 103. – P. 305–314.

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2019.