Влияние микрогравитации на тучные клетки как полифункциональный элемент иммунной системы

Представленный обзор литературы, посвящен проблеме влияния одного из факторов космического полета – микрогравитации на различные элементы иммунной системы, в частности, тучные клетки (ТК). ТК являются одним из звеньев врожденного иммунитета. Они располагаются в тканях почти повсеместно, преимущественно в непосредственной близости от кровеносных сосудов и нервов. Их численность преобладает в органах и тканях, находящихся на границе с внешней средой. ТК одними из первых взаимодействуют с вторгающимися патогенами. Активация ТК приводит к высвобождению широкого спектра биологически активных веществ, таких как гепарин, гистамин, химаза, триптаза, лейкотриены LTB4, LTD4, PDG2 и PAF, цитокины IL-10, IL-8, IL-5, IL-3, IL-1, GM-CSF, TGF-β, VEGF и фактор некроза опухолей TNF-α. ТК вносят вклад в развитие аллергии, сердечно-сосудистой и онкопатологии, заболеваний органов дыхания, желудочно-кишечного тракта. Многочисленные факторы космического полета, такие как микрогравитация, оказывают негативное влияние на иммунную систему. Такое воздействие затрагивает весь процесс развития иммунных клеток (макрофагов, моноцитов, нейтрофилов, Т- и В-лимфоцитов, дендритных клеток и NK-клеток), включая их пролиферацию, дифференцировку, активацию, метаболизм. Приводятся данные о том, что влияние микрогравитации на ТК проявляется в виде усиления апоптоза, снижения пролиферации, а также нарушения процессов дегрануляции и секреции цитокинов. Морфофункциональные изменения иммунных клеток, включая ТК в условиях микрогравитаии соотносятся с изменениями, возникающими в других клетках млекопитающих и заключаются в индуцировании апоптоза, изменениях цитоскелета, нарушениях сигнальных путей, клеточной дифференцировки, роста, пролиферации, миграции и адгезии.

1. Afshinnekoo E., Scott R.T., MacKay M.J., Pariset E. et al. Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration. Cell. 2020 Nov 25;183(5):1162-1184. doi: 10.1016/j.cell.2020.10.050

2. Agis H., Füreder W., Bankl H.C., Kundi M. et al. Comparative immunophenotypic analysis of human mast cells, blood basophils and monocytes. Immunology. 1996 Apr;87(4):535-43. doi: 10.1046/j.1365-2567.1996.493578.x. PMID: 8675206; PMCID: PMC1384130.

3. Aoki R., Kawamura T., Goshima F., Ogawa Y. et al. Mast cells play a key role in host defense against herpes simplex virus infection through TNF-α and IL-6 production. J Invest Dermatol. 2013 Sep;133(9):2170-9. doi: 10.1038/jid.2013.150. Epub 2013 Mar 25. PMID: 23528820.

4. Atiakshin D, Kostin A, Shishkina V, Burtseva A, Buravleva A, Volodkin A, Elieh-Ali-Komi D, Buchwalow I, Tiemann M. Space-Flight- and Microgravity-Dependent Alteration of Mast Cell Population and Protease Expression in Digestive Organs of Mongolian Gerbils. Int J Mol Sci. 2023 Sep 2;24(17):13604. doi: 10.3390/ijms241713604

5. Bigley AB, Agha NH, Baker FL, Spielmann G, Kunz HE, Mylabathula PL, et al. NK cell function is impaired during long-duration spaceflight. J. Appl. Physiol. 2019, 126, 842–853. doi: 10.1152/japplphysiol.00761.2018

6. Borchers A.T., Keen C.L., Gershwin M.E. Microgravity and immune responsiveness: implications for space travel. Nutrition. 2002 Oct;18(10):889-98. doi: 10.1016/s0899-9007(02)00913-9. PMID: 12361784.

7. Brojakowska A, Kour A, Thel MC, Park E, Bisserier M, Garikipati VNS, et al. Retrospective analysis of somatic mutations and clonal hematopoiesis in astronauts. Commun. Biol. 2022, 5, 828. doi: 10.1038/s42003-022-03777-z

8. Calcagno G, Jeandel J, Jean-Pol Frippiat, Kaminski S. Simulated Microgravity Disrupts Nuclear Factor kB Signaling and Impairs Murine Dendritic Cell Phenotype and Function. Int. J. Mol. Sci. 2023, 24, 1720. doi: 10.3390/ijms24021720

9. Cardamone C., Parente R., Feo G.D., Triggiani M. Mast cells as effector cells of innate immunity and regulators of adaptive immunity. Immunol Lett. 2016 Oct;178:10-4. doi: 10.1016/j.imlet.2016.07.003. Epub 2016 Jul 5. PMID: 27393494.

10. Cogoli A. Gravitational physiology of human immune cells: a review of in vivo, ex vivo and in vitro studies //Journal of gravitational physiology: a journal of the International Society for Gravitational Physiology. – 1996. – Vol.3. № 1. – P. 1-9.

11. Corydon TJ, Schulz H, Richter P, Strauch SM, Böhmer M, Ricciardi DA, et al. Current Knowledge about the Impact of Microgravity on Gene Regulation. Cells [Internet]. 2023;12(7):1043. doi: 10.3390/cells12071043

12. Crucian B.E., Choukèr A., Simpson R.J., Mehta S. et al. Immune System Dysregulation During Spaceflight: Potential Countermeasures for Deep Space Exploration Missions. Front. Immunol. 2018. 9:1437. doi: 10.3389/fimmu.2018.01437.

13. Crucian B., Johnston S., Mehta S., Stowe R. et al. A case of persistent skin rash and rhinitis with immune system dysregulation onboard the International Space Station. J Allergy Clin Immunol Pract. 2016 Jul-Aug;4(4):759-762.e8. doi: 10.1016/j.jaip.2015.12.021. Epub 2016 Mar 29. PMID: 27036643.

14. Crucian B, Stowe R, Mehta S, Uchakin P, Quiriarte H, Pierson D, Sams C. Immune system dysregulation occurs during short duration spaceflight on board the space shuttle. J Clin Immunol. 2013 Feb;33(2):456-65. doi: 10.1007/s10875-012-9824-7. Epub 2012 Oct 26. PMID: 23100144.

15. Crucian B, Stowe R, Quiriarte H, Pierson D, Sams C. Monocyte phenotype and cytokine production profiles are dysregulated by short-duration space-flight. Aviat. Sp. Environ. Med. 2011, 82, 857–862. doi: 10.3357/asem.3047.2011

16. da Silva E.Z., Jamur M.C., Oliver C.J. Mast cell function: a new vision of an old cell. // Histochem Cytochem. 2014, 62(10). P. 698-738. doi: 10.1369/0022155414545334.

17. Douaiher J., Succar J., Lancerotto L, Gurish M.F. et al. Development of mast cells and importance of their tryptase and chymase serine proteases in inflammation and wound healing. Adv Immunol. 2014;122:211-52. doi: 10.1016/B978-0-12-800267-4.00006-7. PMID: 24507159; PMCID: PMC4115062.

18. Dwyer D.F., Barrett N.A., Austen K.F. Immunological Genome Project Consortium. Expression profiling of constitutive mast cells reveals a unique identity within the immune system. Nat Immunol. 2016 Jul;17(7):878-87. doi: 10.1038/ni.3445. Epub 2016 May 2. PMID: 27135604; PMCID: PMC5045264.

19. ElGindi M, Jiranuwat Sapudom, Laws P, Garcia-Sabaté A, Daqaq MF, Teo J.3d microenvironment attenuates simulated microgravitymediated changes in t cell transcriptome. Cell. Mol. Life Sci. 2022, 79, 508. doi: 10.1007/s00018-022-04531-8

20. ElGindi M, Sapudom J, Ibrahim IH, Al-Sayegh M, Chen W, Garcia-Sabaté A, et al. May the Force Be with You (Or Not): The Immune System under Microgravity. Cells. 2021 Jul 30;10(8):1941. doi: 10.3390/cells10081941

21. Gschwandtner M., Paulitschke V., Mildner M., Brunner P.M. et al. Proteome analysis identifies L1CAM/CD171 and DPP4/CD26 as novel markers of human skin mast cells. Allergy. 2017 Jan;72(1):85-97. doi: 10.1111/all.12919. Epub 2016 May 25. PMID: 27091730.

22. Guignandon A, Akhouayri O, Usson Y, Rattner A, Laroche N, Lafage-Proust MH, et al. Focal contact clustering in osteoblastic cells under mechanical stresses: microgravity and cyclic deformation. Cell Commun Adhes. 2003 Mar-Apr;10(2):69-83. doi: 10.1080/cac.10.2.69.83

23. Herranz R., Anken R., Boonstra J., Braun M. et al. Ground-based facilities for simulation of microgravity: Organism-specific recommendations for their use, and recommended terminology. Astrobiology. 2013. 13(1):1–17. doi: 10.1089/ast.2012.0876.

24. Ierna M.X., Scales H.E., Saunders K.L., Lawrence C.E. Mast cell production of IL-4 and TNF may be required for protective and pathological responses in gastrointestinal helminth infection. Mucosal Immunol. 2008 Mar;1(2):147-55. doi: 10.1038/mi.2007.16. Epub 2008 Jan 23. PMID: 19079172.

25. Jimeénez M., Cervantes-Garcı́a D., Córdova-Dávalos L.E., Pérez-Rodrı́guez M.J. et al. Responses of Mast Cells to Pathogens: Beneficial and Detrimental Roles. Front. Immunol. 2021. 12:685865. doi: 10.3389/fimmu.2021.685865.

26. Jindal S., Manjari M., Girdhar M. Role of mast cells in leprosy-A study of 62 cases. J. Evolution Med. Dent. Sci. 2017;6(74):5328-5331, DOI: 10.14260/Jemds/2017/1157.

27. Kim M., Jang G., Kim K.S., Shin J. Detrimental effects of simulated microgravity on mast cell homeostasis and function. Front Immunol. 2022 Dec 16;13:1055531. doi: 10.3389/fimmu.2022.1055531. PMID: 36591304; PMCID: PMC9800517.

28. Kocabas C.N., Yavuz A.S., Lipsky P.E., Metcalfe D.D. et al. Analysis of the lineage relationship between mast cells and basophils using the c-kit D816V mutation as a biologic signature. J Allergy Clin Immunol. 2005 Jun;115(6):1155-61. doi: 10.1016/j.jaci.2005.02.030. PMID: 15940128.

29. Komi D.E.A., Khomtchouk K., Santa Maria P.L. A Review of the contribution of mast cells in wound healing: involved molecular and cellular mechanisms. Clin Rev Allergy Immunol. 2020 Jun;58(3):298-312. doi: 10.1007/s12016-019-08729-w. PMID: 30729428.

30. Komi D.E.A., Mortaz E., Amani S., Tiotiu A. et al. The Role of Mast Cells in IgE-Independent Lung Diseases. Clin Rev Allergy Immunol. 2020 Jun;58(3):377-387. doi: 10.1007/s12016-020-08779-5. PMID: 32086776; PMCID: PMC7244458.

31. Komi D.E.A., Wöhrl S, Bielory L. Mast Cell Biology at Molecular Level: a Comprehensive Review. Clin Rev Allergy Immunol. 2020 Jun;58(3):342-365. doi: 10.1007/s12016-019-08769-2. PMID: 31828527.

32. Li Q, Mei Q, Huyan T, Xie L, Che S, Yang H, et al. Effects of simulated microgravity on primary human NK cells. Astrobiology 2013, 13, 703–714 doi: 10.1089/ast.2013.0981

33. Ludtka C, Moore E, Allen JB. The effects of simulated microgravity on macrophage phenotype. Biomedicines 2021, 9, 1205. doi: 10.3390/biomedicines9091205

34. Lv H., Yang H., Jiang C., Shi J. et al. Microgravity and immune cells. J R Soc Interface. 2023 Feb;20(199):20220869. doi: 10.1098/rsif.2022.0869. Epub 2023 Feb 15. PMID: 36789512; PMCID: PMC9929508.

35. Metcalfe D.D., Baram D., Mekori Y. A. Mast cells. Physiol Rev. 1997 Oct;77(4):1033-79. doi: 10.1152/physrev.1997.77.4.1033. PMID: 9354811.

36. Morey-Holton E.R., Globus R.K., Kaplansky A., Durnova, G.N. The hindlimb unloading rat model: literature overview, technique update and comparison with space flight data. Advances in space biology and medicine, 2005. 10, 7–40.

37. Morukov B., Rykova M., Antropova E., Berendeeva T. et al. T-cell immunity and cytokine production in cosmonauts after long-duration space flights / Acta Astronautica. 2011. Vol. 68. Is. 7–8. P. 739–746.

38. Mukai K., Tsai M., Starkl P., Marichal T. et al. IgE and mast cells in host defense against parasites and venoms. Semin Immunopathol. 2016 Sep;38(5):581-603. doi: 10.1007/s00281-016-0565-1. Epub 2016 May 25. PMID: 27225312; PMCID: PMC5010491.

39. Nakajima S., Bamba N., Hattori T. Histological aspects and role of mast cells in Helicobacter pylori-infected gastritis. Aliment Pharmacol Ther. 2004 Jul;20 Suppl 1:165-70. doi: 10.1111/j.1365-2036.2004.01974.x. PMID: 15298623.

40. Nguyen H.P., Tran P.H., Kim K.S., Yang SG. The effects of real and simulated microgravity on cellular mitochondrial function. NPJ Microgravity. 2021 Nov 8;7(1):44. doi: 10.1038/s41526-021-00171-7. PMID: 34750383; PMCID.

41. Paul AM, Mhatre SD, Cekanaviciute E, Schreurs AS, Tahimic CGT, Globus RK, et al. Neutrophil-to-Lymphocyte Ratio: A Biomarker to Monitor the Immune Status of Astronauts. Frontiers in Immunology. 2020 Nov 2;11. 1–12. doi: 10.3389/fimmu.2020.564950

42. Paulsen K, Tauber S, Goelz N, Simmet DM, Engeli S, Birlem M, et al. Severe disruption of the cytoskeleton and immunologically relevant surface molecules in a human macrophageal cell line in microgravity—Results of an in vitro experiment on board of the Shenzhou-8 space mission. Acta Astronaut. 2014, 94, 277–292.

43. Pietsch J., Bauer J., Egli M., Infanger M. et al. The effects of weightlessness on the human organism and mammalian cells. Curr Mol Med. 2011 Jul;11(5):350-64. doi: 10.2174/156652411795976600. PMID: 21568935.

44. Piliponsky AM, Acharya M, Shubin NJ. Mast Cells in Viral, Bacterial, and Fungal Infection Immunity. Int J Mol Sci. 2019 Jun 12;20(12):2851. doi: 10.3390/ijms20122851. PMID: 31212724; PMCID: PMC6627964.

45. Renga G., Moretti S., Oikonomou V., Borghi M. et al. IL-9 and Mast Cells Are Key Players of Candida albicans Commensalism and Pathogenesis in the Gut. Cell Rep. 2018 May 8;23(6):1767-1778. doi: 10.1016/j.celrep.2018.04.034. PMID: 29742432; PMCID: PMC5976578.

46. Rooney B.V., Crucian B.E., Pierson D.L., Laudenslager M.L. et al. Herpes Virus Reactivation in Astronauts During Spaceflight and Its Application on Earth. Front. Microbiol. 2019. 10:16. doi: 10.3389/fmicb.2019.00016.

47. Rykova M.P., Antropova E.N., Larina I.M., Morukov B.V. Humoral and cellular immunity in cosmonauts after the ISS missions // Acta Astronautica. Vol. 63. Is.7-10. P. 697–705.

48. Saito H., Nakajima T., Matsumoto K. Human mast cell transcriptome project. Int Arch Allergy Immunol. 2001 May;125(1):1-8. doi: 10.1159/000053790. PMID: 11385282.

49. Shefler I., Salamon P., Mekori Y.A. Extracellular Vesicles as Emerging Players in Intercellular Communication: Relevance in Mast Cell-Mediated Pathophysiology. Int J Mol Sci. 2021 Aug 25;22(17):9176. doi: 10.3390/ijms22179176. PMID: 34502083; PMCID: PMC8431297.

50. Sonnenfeld G. Space flight, microgravity, stress, and immune responses. Adv. Space Res. Off. J. Comm. Space Res. COSPAR 1999, 23, 1945–1953. (doi:10.1016/S0273-1177(99)00455-X.

51. Spatz JM, Fulford MH, Tsai A, Gaudilliere D, Hedou J, Ganio E, et al. Human immune system adaptations to simulated microgravity revealed by single-cell mass cytometry. Sci. Rep. 2021, 11, 11872. doi: 10.1038/s41598-021-90458-2

52. Stervbo U., et al. Gravitational stress during parabolic flights reduces the number of circulating innate and adaptive leukocyte subsets in human blood. PLoS ONE 2019, 13, e020627. doi: 10.1371/journal.pone.0206272.

53. Sundstrom J.B., Ellis J.E., Hair G.A., Kirshenbaum A.S. et al. Human tissue mast cells are an inducible reservoir of persistent HIV infection. Blood. 2007 Jun 15;109(12):5293-300. doi: 10.1182/blood-2006-11-058438. Epub 2007 Mar 9. PMID: 17351109; PMCID.

54. Torres-Atencio I., Campble A., Goodridge A., Martin M. Uncovering the Mast Cell Response to Mycobacterium tuberculosis. Front Immunol. 2022 Jun 2;13:886044. doi: 10.3389/fimmu.2022.886044. PMID: 35720353; PMCID: PMC9201906.

55. Vahlensieck C, Cora Sandra Thiel, Zhang Y, Huge A, Ullrich O. Gravitational force-induced 3d chromosomal conformational changes are associated with rapid transcriptional response in human t cells. Int. J. Mol. Sci. 2021, 22, 9426. doi: 10.3390/ijms22179426

56. Valent P., Akin C., Hartmann K., Nilsson G. et al. Mast cells as a unique hematopoietic lineage and cell system: From Paul Ehrlich's visions to precision medicine concepts. Theranostics. 2020; 10(23):10743-10768. doi:10.7150/thno.46719.

57. Vukman K.V., Försönits A., Oszvald Á., Tóth EÁ. et al. Mast cell secretome: Soluble and vesicular components. Semin Cell Dev Biol. 2017 Jul;67:65-73. doi: 10.1016/j.semcdb.2017.02.002. Epub 2017 Feb 9. PMID: 28189858.

58. Zayzafoon M., Meyers V.E., McDonald J.M. Microgravity: the immune response and bone. Immunol. Rev. 2005. 208, 267–280.