EFFECT OF IRON-MOLYBDENUM NANOCLUSTER POLYOXOMETALATES ON THE FUNCTIONAL ACTIVITY OF MACROPHAGES AND THE STATE OF BONE MARROW ERYTHROBLASTIC ISLANDS
https://doi.org/10.15789/1563-0625-EOI-3190
Abstract
Abstract
The aim of this study was to determine the mechanisms of action of {Mo72Fe30} on erythropoiesis and hematological parameters *in vitro* and *in vivo*. The obtained results showed that neither the nanocluster polyoxometalate {Mo72Fe30} nor its destruction products (low-molecular-weight iron and molybdenum-containing ions) affected the activity of non-specific esterase in the cytoplasm of central macrophages of bone marrow erythroblastic islands, thus indicating no disruption of endotoxin and xenobiotic detoxification processes carried out by these macrophages. However, administration of the studied substances resulted in a decrease in macrophage phagocytic capacity without altering cellular involvement in phagocytosis.
Analysis of erythroblastic island cultures revealed the following patterns: administration of {Mo72Fe30} and its destruction products (PD) accelerated erythroid cell maturation within the erythroblastic island corona. At 24 hours after their administration, a decrease in the number of class 3 and involutive erythroblastic islands was observed due to accelerated maturation and dissociation of erythroblastic islands. This process was confirmed by an increase in the number of erythroid cells in the myelogram at 24 hours after these substances administration. The simultaneous increase in the number of reconstructing erythroblastic islands in the groups treated with the polyoxometalate and its PD suggests the development of an additional wave of erythropoiesis within the island corona. On day 2 after administration of {Mo72Fe30}, there was an increase in the number of proliferating erythroblastic islands of the class 2 and 3, while the number of class 1 islands remained unchanged. This is attributed to the involvement of new macrophages into erythropoiesis and active erythroid cells proliferation. On day 3, a shift towards a more mature proliferating erythroblastic islands of the class 2 was observed. These data indicate the acceleration of erythrocyte maturation within erythroblastic islands after 3 days of the {Mo72Fe30} administration. A similar trend was observed with the PD administration, although the erythropoiesis-accelerating effect was less pronounced.
Analysis of rat bone marrow myelograms revealed an increase in bone marrow cellularity after seven days of administration of the studied substances ({Mo72Fe30} and PD). This increase was attributed, in part, to an increase in the number of erythroid cells and reticulocytes.
These data are consistent with peripheral blood parameters in rats. A statistically significant increase in erythrocyte count, hemoglobin levels, and hematocrit values was observed following administration of the studied substances ({Mo72Fe30} and PD).
The experimental results suggest a potential stimulatory effect on erythroid lineage development.
About the Authors
A. A. TitovaRussian Federation
Junior Researcher
M. O. Tonkushina
Russian Federation
Ph. D., Senior Researcher
A. A. Ostroushko
Russian Federation
Dr. Sc., Professor, Chief Researcher and Head of Department
M. V. Ulitko
Russian Federation
Ph. D., Аssociate professor, Director of the Department
S. A. Brilliant
Russian Federation
Ph.D, researcher
I. G. Danilova
Russian Federation
Dr. Sc., Associate Professor
References
1. Abrashova T. V., Guschin A. Ya., Kovaleva M. A., Rybakova A.V., Selezneva A. I. Handbook. Physiological, biochemical and biometric indicators of the norm of experimental animals. Saint Petersburg: LEMA Publishing House. 2013. P. 116.
2. Balabekova M. K., Nurmukhambetov A. N., Udartseva T. P., Nurgalieva T. K. Peripheral blood parameters and cellular composition of bone marrow in rats with experimental inflammation // Bulletin of the Kazakh National Medical University. 2010. V 5–3. P. 281–286.
3. Brilliant S.A., Yshkov B.G. The study hemoglobine
4. spectrum of rats bone marrow with post-hemorrhagic anemia.
5. Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical
6. Academic Science. 2018, Vol. 15, no. 4, pp. 570–576.
7. Influence of iron-molybdenum nanocluster polyoxometalates on the apoptosis of blood leukocytes and the level of heat-shock proteins in the cells of thymus and spleen in rats / I. G. Danilova, I. F. Gette, S. Y. Medvedeva [et al.] // Nanotechnologies in Russia. – 2016. – Vol. 11, No. 9-10. – DOI 10.1134/S1995078016050049. – EDN XFMHUH.
8. Drapkina O.M., Avalueva E.B.,
9. Bakulin I.G., Vinogradova M.A. et al. Management of patients with
10. iron deficiency anemia at the stage of primary health care: a practical
11. guide. M.; 2022. 88 p. (in Russian). DOI: 10.15829/ROPNIZ-zda-2022
12. Zakharov, I.uM., Mel'nikov, I. I.u, & Rassokhin, A. G. (1984).
13. Issledovanie éritropoéza modifitsirovannym metodom vydeleniia éritroblasticheskikh ostrovkov kostnogo mozga [Erythropoiesis studied by a modified method of isolating bone marrow erythroblastic islands]. Gematologiia i transfuziologiia, 29(4), 52–54.
14. Zakharov, I.uM., Mel'nikov, I. I.u, & Rassokhin, A. G. (1990). Klassifikatsiia éritroblasticheskikh ostrovkov kostnogo mozga s uchetom izmeneniĭ ikh kletochnogo sostava [Classification of erythroblastic islets of the bone marrow and the study of their cellular composition]. Arkhiv anatomii, gistologii i embriologii, 98(5), 38–42.
15. Zakharov Yu.M. New approaches to the study of erythropoiesis
16. in animals and humans. Izvestiya Chelyabinskogo nauchnogo tsentra
17. UrO RАN. 2(11): 99-103. 2001
18. Zakharov Yu.M. Erythroblastic islet: a monograph / Yu. M. Zakharov, A. G. Rassokhin. Moscow : Meditsina Publ., 2002. 279, [1] p.
19. Kost E. Handbook of clinical laboratory research methods // M.: Medicine. 1975. (178).
20. Influence of Nanocluster Molybdenum Polyoxometalates on the Morphofunctional State of Fibroblasts in Culture / A. A. Ostroushko, M. V. Ulitko, M. O. Tonkushina [et al.] // Nanotechnologies in Russia. – 2018. – Vol. 13, No. 1-2. – DOI 10.1134/S199507801801010X. – EDN YBNRJR.
21. Ostroushko, A.A., Gette, I.F., Brilliant, S.A. et al. Application of nanocluster iron–molybdene polyoxometalates for correction of experimental posthemorrhagic anemia. Nanotechnol Russia 14, 159–164 (2019). https://doi.org/10.1134/S1995078019020101
22. Patent No. 2671077 C1 Russian Federation, IPC G09B 23/28, A61K 33/26, A61P 7/06. method of correction of posthemorrhagic anemia : No. 2017124300 : application 07.07.2017 : published 29.10.2018 / A. A. Ostroushko, M. O. Tonkushina, I. D. Gagarin [et al.] ; applicant Federal State Autonomous Educational Institution of Higher Education "Ural Federal University named after the first President of Russia B.N. Yeltsin" (UrFU), Federal State Budgetary Institution of Science Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences (IIF Ural Branch of the Russian Academy of Sciences).
23. Abbaspour N., Hurrell R., Kelishadi R. Review on iron and its importance for human health // Journal of research in medical sciences: the official journal of Isfahan University of Medical Sciences. 2014. V. 2 (19). P. 164.
24. Almeida A. F., Miranda M. S., Vinhas A., Gonçalves A. I., Gomes M. E., Rodrigues M. T. Controlling Macrophage Polarization to Modulate Inflammatory Cues Using Immune-Switch Nanoparticles // International Journal of Molecular Sciences. 2022. V. 23 (23). P. 15125.
25. Anaemia in women and children [Электронный ресурс]. URL: https://www.who.int/data/gho/data/themes/topics/anaemia_in_women_and_children (дата обращения: 26.12.2024).
26. Corna G., Campana L., Pignatti E., Castiglioni A., Tagliafico E., Bosurgi L., Campanella A., Brunelli S., Manfredi A. A., Apostoli P., Silvestri L., Camaschella C., Rovere-Querini, P. Polarization dictates iron handling by inflammatory and alternatively activated macrophages // Haematologica. 2010. V. 11 (95). P. 1814–1822.
27. Dhingra V. K., Gupta R. K. P., Sadana J. R. Demonstration of acid alpha naphthyl acetate esterase activity in bovine lymphocytes and monocytes or macrophages // Research in Veterinary Science. 1982. V. 1 (33). P. 26–30.
28. Gaetano C., Massimo L., Alberto M. Control of iron homeostasis as a key component of macrophage polarization // Haematologica. 2010. V. 11 (95). P. 1801–1803.
29. Gammella E., Buratti, P., Cairo, G., Recalcati, S. Macrophages: central regulators of iron balance // Metallomics. 2014. V. 8 (6). P. 1336–1345.
30. Grech B. J. Mechanistic insights into the treatment of iron-deficiency anemia and arthritis in humans with dietary molybdenum // European Journal of Clinical Nutrition. 2021. V. 8 (75). P. 1170–1175.
31. Hayhoe F. G. J., Quaglino D. 1980. Haematological cytochemistry. Edinburgh; N.Y.: Churchill Livingstone. P. 336.
32. Jackson J. 2016. Chapter 3: Immunology: Host Responses to Biomaterials. In: Lee SJ, Atala A, Yoo J (editors), In Situ Tissue Regeneration: Host Cell Recruitment and Biomaterial Design. Elsevier/Academic Press. P. 35.
33. Laskar A., Eilertsen J., Li W., Yuan X. M. SPION primes THP1 derived M2 macrophages towards M1-like macrophages // Biochemical and Biophysical Research Communications. 2013. V. 4 (441). P. 737–742.
34. Lucarelli, M., Gatti, A. M., Savarino, G., Quattroni, P., Martinelli, L., Monari, E., & Boraschi, D. Innate defence functions of macrophages can be biased by nano-sized ceramic and metallic particles // European cytokine network. 2004. V. 4 (15). P. 339–346.
35. Martinez-Torres V., Torres N., Davis J. A., Corrales-Medina F. F. Anemia and Associated Risk Factors in Pediatric Patients // Pediatric Health, Medicine and Therapeutics. 2023. V. 14. P. 267–280.
36. Mendel R. R. Metabolism of Molybdenum Metal Ions in Life Sciences / под ред. L. Banci, Dordrecht: Springer Netherlands, 2013.P. 503–528.
37. Miao X., Leng X., Zhang Q. The Current State of Nanoparticle-Induced Macrophage Polarization and Reprogramming Research // International Journal of Molecular Sciences. 2017. V. 2 (18). P. 336.
38. Müller A., Sarkar S., Shah S. Q., Bögge, H., Schmidtmann M., Kögerler P., Hauptfleisch, B., Trautwein A. X., Schünemann V. V. Archimedean Synthesis and Magic Numbers: «Sizing» Giant Molybdenum-Oxide-Based Molecular Spheres of the Keplerate Type // Angewandte Chemie International Edition. 1999. V. 21 (38). P. 3238–3241.
39. Rampton D., Folkersen J., Fishbane S., Hedenus M., Howaldt S., Locatelli F., Patni S., Szebeni J., Weiss G. Hypersensitivity reactions to intravenous iron: guidance for risk minimization and management // Haematologica. 2014. V. 11 (99). P. 1671–1676.
40. Recalcati S., Locati M., Marini A., Santambrogio P., Zaninotto F., De Pizzol M., Zammataro L., Girelli D., Cairo G. Differential regulation of iron homeostasis during human macrophage polarized activation // European Journal of Immunology. 2010. V. 3 (40). P. 824–835.
41. Rogler G. Immune Cells: Monocytes and Macrophages под ред. D. C. Baumgart, Cham: Springer International Publishing, 2017.P. 119–122.
42. Shafer A. W., Marlow A. A. Toxic Reaction to Intramuscular Injection of Iron // New England Journal of Medicine. 1959. V. 4 (260). P. 180–180.
43. Sharma L., Wu W., Dholakiya S. L., Gorasiya S., Wu, J., Sitapara R., Patel V., Wang M., Zur M., Reddy S., Siegelaub N., Bamba K., Barile F. A., Mantell L. L. Assessment of Phagocytic Activity of Cultured Macrophages Using Fluorescence Microscopy and Flow Cytometry Methods in Molecular Biology / под ред. I. Vancurova, New York, NY: Springer New York, 2014.P. 137–145.
44. Soares M. P., Hamza I. Macrophages and Iron Metabolism // Immunity. 2016. V. 3 (44). P. 492–504.
45. Terriere L. C. Induction of Detoxication Enzymes in Insects // Annual Review of Entomology. 1984. V. 1 (29). P. 71–88.
46. Wang L., Zhang H., Sun L. et al. Manipulation of macrophage polarization by peptide-coated gold nanoparticles and its protective effects on acute lung injury // J. Nanobiotechnol. 2020. V. 18 (1). P. 38
47. Zanganeh S., Hutter G., Spitler R., Lenkov O., Mahmoudi M., Shaw A., Pajarinen J.S., Nejadnik H., Goodman S., Moseley M. Iron oxide nanoparticles inhibit tumour growth by inducing pro-inflammatory macrophage polarization in tumour tissues // Nat. Nanotechnol. 2016. V. 11. P. 986–994.
48. Zvereva E. Activity and heavy metal resistance of non-specific esterases in leaf beetle Chrysomela lapponica from polluted and unpolluted habitats // Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology. 2003. V. 4 (135). P. 383–391.
Supplementary files
![]() |
1. Рисунок_3. EU | |
Subject | ||
Type | Other | |
Download
(15KB)
|
Indexing metadata ▾ |
![]() |
2. 3190 | |
Subject | ||
Type | Other | |
Download
(3MB)
|
Indexing metadata ▾ |
Review
For citations:
Titova A.A., Tonkushina M.O., Ostroushko A.A., Ulitko M.V., Brilliant S.A., Danilova I.G. EFFECT OF IRON-MOLYBDENUM NANOCLUSTER POLYOXOMETALATES ON THE FUNCTIONAL ACTIVITY OF MACROPHAGES AND THE STATE OF BONE MARROW ERYTHROBLASTIC ISLANDS. Medical Immunology (Russia). (In Russ.) https://doi.org/10.15789/1563-0625-EOI-3190