Mast Cells as an Active Component of Wound Repair Process

The successes of modern surgery of wounds are impossible without understanding the changes in intercellular and cell-matrix interactions, in this connection the latest data on the role of mast cells in various pathological states deserve special attention. Mast cells play a key role in tissue repair. Their maximum representation is found in the skin, mucous membranes of the respiratory system, gastrointestinal tract. Mast cells are activated immediately after skin damage and are involved in all phases of the wound process. When tissue damage or adverse effects from mast cells are released, a whole arsenal of inflammatory mediators, proteases, growth factors that trigger a cascade of reactions, including the inflammatory process. Serine proteases efficiently remodel elements of the extracellular matrix, which is necessary for the transition to the next stage of wound healing. The multifunctionality of mast cells is manifested by the release of both proinflammatory and anti-inflammatory and immunosuppressive cytokines, which is an important clinical aspect, since an incorrect treatment tactic contributes to the chronic wound process. Synthesis of collagen by fibroblasts and angiogenesis are the result of complex molecular-cell events with the direct involvement of mast cells. In the late stages of the wound process during re-epithelialization, their mediators can stimulate keratinocytes to restore the epidermal barrier. Studying the effects of mast cells with slow regeneration due to diabetes mellitus, ischemia, tissue denervation, and microcirculation disturbance opens up prospects in the treatment of long-term non-healing wounds with socially significant diseases. Thus, already known data and further fundamental studies of mast cells allow us to consider them as a biomarker of the dynamics and severity of the wound process, and as a target for regulating the wound process at different stages.

тучные клетки, раневой процесс, репарация тканей, mast cells, wound process, tissue repair

1. Алексеева Н. Т. Гистопланиметрическая характеристика асептического раневого процесса при различных методиках регионального воздействия. Медицинские науки. 2014; 10: 817-821.

2. Алексеева Н. Т. Участие клеточного компонента в регенерации раны. Журнал анатомии и гистопатологии. 2014; 1(3): 9-15.

3. Алексеева Н. Т., Никитюк Д. Б. Морфологическая реакция тучных клеток при регенерационном процессе в коже под действием обогащенной тромбоцитами плазмы крови. Вопросы морфологии XXI века. 2015: 1-6.

4. Атякшин Д. А., Бурцева А. С., Алексеева Н. Т. Триптаза как полифункциональный компонент секретома тучных клеток. Журнал анатомии и гистопатологии. 2017; 1(6): 121-132.

5. Лазарев А. Ф., Бобров И. П., Черданцева Т. М., Климачев В. В., Брюханов В. М., Авдалян А. М., Лубенников В. А., Гервальд В. Я. Тучные клетки и опухолевый рост. Сибирский онкологический журнал. 2011; 46(4): 59-63.

6. Andrade M. V., Iwaki S., Ropert C., et al. Amplification of cytokine production through synergistic activation of NFAT and AP-1 following stimulation of mast cells with antigen and IL-33. Eur J Immunol. 2011; 41:760-772. [PubMed: 21308681]

7. Atiakshin D., Buchwalow I., Samoilova V., Tiemann M. Tryptase as a polyfunctional component of mast cells. Histochem Cell Biol. 2018 May;149(5):461-477.

8. Atiakshin D., et al. Characterization of mast cell populations using different methods for their identification. Histochemistry and Cell Biology. 2017;147(6): 683-694.

9. Bowrey P. F., King J., Magarey C., Schwartz P., Marr P., Bolton E., Morris D. L. Histamine, mast cells and tumour cell proliferation in breast cancer: does preoperative cimetidine administration have an effect? Br J Cancer. 2000; 82: 167-70.

10. Crivellato E., Nico B., Ribatti D. Mast cells and tumour angiogenesis: new insight from experimental carcinogenesis. Cancer Lett. 2008; 269: 1-6.

11. Crivellato E., Travan L., Ribatti D. The phylogenetic profile of mast cells. Methods Mol Biol. 2015; 1220: 11-27.

12. Depinay N., Hacini F., Beghdadi W., et al. Mast cell-dependent down-regulation of antigen-specific immune responses by mosquito bites. J Immunol. 2006; 176:4141-4146. [PubMed: 16547250]

13. Desmouli`ere A., Geinoz A., Gabbiani F., Gabbiani G. Transforming growth factor-β1 induces α-smooth muscle actin expression in granulation tissue myofibrobalsts and in quiescent and growing cultured fibroblasts. J Cell Biol 1993; 122: 103-111.

14. Di Nardo A., Yamasaki K., Dorschner R. A., et al. Mast cell cathelicidin antimicrobial peptide prevents invasive group A Streptococcus infection of the skin. J Immunol. 2008; 180: 7565-7573. [PubMed: 18490758]

15. Galli S. J., Nakae S., Tsai M. Mast cells in the development of adaptive immune responses. Nat Immunol. 2005; 6:135-142. [PubMed: 15662442]

16. Greenhalgh D. G. Models of wound healing. J Burn Care Rehabil. 2005; 26: 293-305. [PubMed: 16006836]

17. Hart J. Inflammation 1: its role in the healing of acute wounds. J Wound Care 2002; 11: 205-209.

18. Harunari N., Zhu K. Q., Armendariz R. T., et al. Histology of the thick scar on the female, red Duroc pig: final similarities to human hypertrophic scar. Burns. 2006; 32: 669-677. [PubMed: 16905264]

19. Hundley T. R., Gilfillan A. M., Tkaczyk C., et al. Kit and FcεRI mediate unique and convergent signals for release of inflammatory mediators from human mast cells. Blood. 2004; 104: 2410-2417. [PubMed: 15217825]

20. Iba Y., Shibata A., Kato M., et al. Possible involvement of mast cells in collagen remodeling in the late phase of cutaneous wound healing in mice. Int Immunopharmacol. 2004; 4:1873-1880. [PubMed: 15531302]

21. Jeong W. I., Lee C. S., Park S. J., et al. Kinetics of macrophages, myofibroblasts and mast cells in carbon tetrachloride-induced rat liver cirrhosis. Anticancer Res. 2002; 22:869-877. [PubMed: 12014664]

22. Kagawa S., Matsuo A., Yagi Y., Ikematsu K., Tsuda R., Nakasono I. The time-course analysis of gene expression during wound healing in mouse skin. LegalMed. 2008; 11(2): 70-75.

23. Kihira C., Mizutani H., Asahi K., et al. Increased cutaneous immunoreactive stem cell factor expression and serum stem cell factor level in systemic scleroderma. J Dermatol Sci. 1998; 20: 72-78. [PubMed: 10342750]

24. Mak K., Manji A., Gallant-Behm C., et al. Scarless healing of oral mucosa is characterized by faster resolution of inflammation and control of myofibroblast action compared to skin wounds in the red Duroc pig model. J Dermatol Sci. 2009; 56:168-180. [PubMed: 19854029]

25. Malaviya R., Ikeda T., Ross E., et al. Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF- α. Nature. 1996; 381: 77-80. [PubMed: 8609993]

26. Miller H. R. P., Pemberton A. D. Tissue-specific expression of mast cell granule serine proteinases and their role in inflammation in the lung and gut. Immunology. 2002; 105: 375-90.

27. Ng M. F. Y. The role of mast cells in wound healing // International wound journal. 2010; 1(7): 55-61.

28. Nienartowicz A., Sobaniec-Lotowska M. E., Jarocka-Cyrta E., Lemancewicz D. Mast cells in neoangiogenesis. Med Sci Monit. 2006; 12: RA53-6.

29. Noli C., Miolo A. The mast cell in wound healing. Vet Dermatol. 2001; 12: 303-313. [PubMed: 11844219]

30. Parslow T. G., Stites D. P., Terr A. I., Imboden J. B., eds. Medical immunology. 10th ed. London, McGraw- Hill, 2001.

31. Ribatti D., et al. Tryptase and chymase are angiogenic in vivo in the chorioallantoic membrane assay. International Journal of Developmental Biology. 2011.

32. Schultz G. S., Davidson J. M., Kirsner R. S., et al. Dynamic reciprocity in the wound microenvironment. Wound Repair Regen. 2011; 19: 134-148. [PubMed: 21362080]

33. Theoharides T. C., Alysandratos K. D., Angelidou A., et al. Mast cells and inflammation. Biochim Biophys Acta. 2012; 1822: 21-33. [PubMed: 21185371].

34. Theoharides T. C., Kempuraj D., Tagen M., Conti P., Kalogeromitros D. Differential releaseofmast cell mediators and the pathogenesis of inflammation. Immunol Rev. 2007; 217: 65-78.

35. Tsai M., Grimbaldeston M., Galli S. J. Mast cells and immunoregulation/immunomodulation. Adv Exp Med Biol. 2011; 716 :186-211. [PubMed: 21713658]

36. Urb M., Sheppard D. C. The role of mast cells in the defence against pathogens. PLoS Pathog. 2012; 8:e1002619. [PubMed: 22577358]

37. Wang J., Ding J., Jiao H., et al. Human hypertrophic scar-like nude mouse model: characterization of the molecular and cellular biology of the scar process. Wound Repair Regen. 2011; 19: 274-285. [PubMed: 21362096]

38. Woolf N. Acute inflammation II: cellular events and chemical mediators. In: Woolf N, editor. Pathology: basic and systemic, 1st ed. London: WB Saunders, 1998: 41-62.

39. Wulff B. C., Wilgus T. A. Mast cell activity in the healing wound: More than meets the eye? Experimental Dermatology. 2013; 8(22): 507-510.

40. Yanashima K., et al. Innate defense regulator IDR-1018 activates human mast cells through G protein-, phospholipase C-, MAPK-and NF-ĸB-sensitive pathways. Immunologic Research. 2017; 65(4): 920-931.

41. Younan G. J., et al. Mast cells are required in the proliferation and remodeling phases of microdeformational wound therapy. Plast reconstr surg. 2011; 6(128): 649e-58e.