Destekleyici bir tedavi olarak mast hücre stabilizatörleri COVID-19 enfeksiyonunda ölümcül inflamatuar yanıtları ve pulmoner komplikasyonların şiddetini hafifletmeye katkıda bulunabilir

Yıl 2020, Sayı: Special Issue on COVID 19, 111 - 118, 20.03.2020

Erkan Kılınç Yasemin Baranoğlu

https://doi.org/10.21673/anadoluklin.720116

Cited By: 10

Öz

SARS-CoV-2 (COVID-19) 
pulmoner sisteme yerleşerek ciddi akut solunum yetmezliği sendromuna yol
açmaktadır. Mast hücreleri vücutta yaygın dağılım gösteren ve pulmoner sistemde
bol miktarda bulunan çok fonksiyonlu bağışıklık hücreleridir. Mast hücreleri
doğal ve kazanılmış bağışıklıkta ve vücudun bağışıklık homeostazının
sürdürülmesinde sitoplazmik granüllerindeki çeşitli mediyatörler aracılığıyla
hayati bir rol oynamaktadır. COVID-19 enfeksiyonu sırasında pro-inflamatuar
sitokin salınımı ve pnömoni ile karakterize ağır akut solunum yetmezliği
özellikle zayıf veya ilişkili kronik hastalıklardan muzdarip bireylerde ölümle
sonuçlanabilmektedir. Bu derlemede COVID-19 semptomları ve mast hücreleri
arasındaki potansiyel ilişkiyi ve destekleyici bir terapötik seçenek olarak
mast hücre stabilizatörlerinin COVID-19 enfeksiyonunda potansiyel kullanımını
tartışmaya çalıştık.

Mast hücreleri, COVID-19 enfeksiyonu sırasında ölümcül
inflamatuar yanıtları ve pulmoner komplikasyonları tetikleyebilen IL-1, IL-6 ve
TNF-α gibi pro-inflamatuar sitokinlerin ve histamin, prostaglandin-D2 ve
lökotrien-C4 gibi bronkokonstriktör mediyatörlerin ana kaynağıdır. SARS-CoV-2,
mast hücrelerini toll-like reseptörleri aracılığıyla veya  IgE-FcεRI’nın çapraz bağlanmasını
tetikleyerek aktive edebilir ve böylece mast hücrelerinden bu mediyatörlerin
salınımına yol açar.

Mast hücrelerinden bu mediyatörlerin SARS-CoV-2 ile
tetiklenmiş anormal üretimi ve salınımı solunum sisteminde inflamasyonu ve
sonuçta pulmoner komplikasyonları daha fazla kötüleştirebilir. Böylece
destekleyici bir tedavi olarak mast hücre stabilizatörlerinin kullanılması
SARS-CoV-2 enfeksiyonundan ölümleri azaltmak amacıyla inflamatuar yanıtları ve
pulmoner komplikasyonları hafifletmek/iyileştirmek için faydalı olabilir.

Anahtar Kelimeler

SARS-CoV-2, COVID-19, mast hücreleri, inflamatuar mediyatörler, mast hücre stabilizatörleri

Mast cell stabilizers as a supportive therapy can contribute to alleviate fatal inflammatory responses and severity of pulmonary complications in COVID-19 infection

Öz

SARS-CoV-2(COVID-19) leads to severe acute
respiratory syndrome by settling the pulmonary system. Mast cells (MCs) are
multifunctional immune cells that are extensively distributed throughout the
body and mostly present in pulmonary system.

MCs play a vital role in acquired and innate
immunity,  and to maintain immune
homeostasis of the body through a wide range of mediators in their cytoplasmic
granules. Severe acute respiratory syndrome with proinflammatory cytokine
release and pneumonia during COVID-19 infection can result in the death, in
particular in debilitated individuals or those suffering from related chronic
disorders. In this review, we attempt to discuss potential relationship between
COVID-19 symptoms and mast cells as well as potential use of mast cell
stabilizers as a supportive therapeutic option in COVID-19 infection.

MCs are main source of pro-inflammatory
cytokines such as IL-1, IL-6 and TNF-α as well as bronchoconstrictor mediators
such as histamine, prostaglandin-D2 and leukotriene-C4 that can lead to fatal
inflammatory responses and pulmonary complications during COVID-19 infection.
SARS-CoV-2 may activate MCs through toll-like receptors or by inducing the
cross-linking of the IgE-FcεRI, thus leading to release of those mediators.
SARS-CoV-2-induced abnormal production and release of these mediators from MCs
can further exacerbate inflammation in respiratory system, consequently
pulmonary complications.

Therefore administration of MC stabilizers as a
supportive therapy may be useful to alleviate inflammatory responses and
pulmonary complications in order to reduce deaths from SARS-CoV-2 infection.

 

Anahtar Kelimeler

SARS-CoV-2, COVID-19, mast cells, inflammatory mediators, mast cell stabilizers

Kaynakça

• 1. Ankaralı H, Ankaralı S, Erarslan N. COVID-19, SARS-CoV2, Infection: current epidemiological analysis and modeling of disease. Anatolian Clinic Journal of Medical Sciences, 2020; 25(Supplement 1): 1-22. 2. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200412-sitrep-83-covid-19.pdf?sfvrsn=697ce98d_4 3. Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med 2020;382(8):727–733. doi:10.1056/NEJMoa2001017 4. Kumar D, Malviya R, Kumar Sharma P. Corona Virus: A review of COVID-19. EJMO 2020; 4(1): 8-25. 5. Shanmugaraj B, Siriwattananon K, Wangkanont K, Phoolcharoen W. Perspectives on monoclonal antibody therapy as potential therapeutic intervention for Coronavirus disease-19 (COVID-19). Asian Pac J Allergy Immunol 2020;38(1):10–18. 6. Guo YR, Cao QD, Hong ZS, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status. Mil Med Res 2020;7(1):11. 7. Chan JF, Yuan S, Kok KH, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020;395(10223):514–523. doi:10.1016/S0140-6736(20)30154-9 8. Lu H, Stratton CW, Tang YW. Outbreak of pneumonia of unknown etiology in Wuhan, China: the mystery and the miracle. J Med Virol 2020;92(4):401–402. 9. Koyuncu Irmak D, Kilinc E, Tore F. Shared fate of meningeal mast cells and sensory neurons in migraine. Front Cell Neurosci 2019;13:136. 10. Theoharides TC, Cochrane DE. Critical role of mast cells in inflammatory diseases and the effect of acute stress. J Neuroimmunol 2004;146(1-2):1-12. 11. Kilinc E, Dagistan Y, Kotan B, Cetinkaya A. Effects of Nigella sativa seeds and certain species of fungi extracts on number and activation of dural mast cells in rats. Physiol Int 2017;104(1):15-24. doi: 10.1556/2060.104.2017.1.8. 12. Tete S, Tripodi D, Rosati M, Conti F, Maccauro G, Saggini A, Salini V, Cianchetti E, Caraffa A, Antinolfi P, Toniato E, Castellani ML, Pandolfi F, Frydas S, Conti P, Theoharides TC. Role of mast cells in innate and adaptive immunity. J Biol Regul Homeost Agents. 2012;26(2):193-201. 13. Kilinc E, Balci CN. An investigation of lung mast cell behavior in a rat model of migraine: Implications for migraine headache. Anatol Clin. 2018; 23(3): 151-156. DOI: 10.21673/anadoluklin.429905. 14. Kilinc E, Guerrero-Toro C, Zakharov A, Vitale C, Gubert-Olive M, Koroleva K, Timonina A, Luz LL, Shelukhina I, Giniatullina R, Tore F, Safronov BV, Giniatullin R. Serotonergic mechanisms of trigeminal meningeal nociception: Implications for migraine pain. Neuropharmacology 2017;116:160-173. doi:10.1016/j.neuropharm.2016.12.024. 15. Kilinc E, Firat T, Tore F, Kiyan A, Kukner A, Tuncel N. Vasoactive intestinal peptide modulates c-fos activity in the trigeminal nucleus and dura mater mast cells in sympathectomized rats. J Neurosci Res 2015;93(4):644-50. 16. Theoharides TC, Alysandratos KD, Angelidou A, et al. Mast cells and inflammation. Biochim Biophys Acta 2012;1822(1):21–33. doi:10.1016/j.bbadis.2010.12.014 17. Kilinc E, Dagistan Y, Cetinkaya A, Tore F. The comparison of effects of applications of compound 48/80 and mast cell mediator suspension on inflammation in rats: A methodological study for acute inflammatory pain. Clin Exp Health Sci 2019; 9: 34-41; - DOI: 10.5152/clinexphealthsci.2018.923 18. Kilinc E, Dagistan Y, Kukner A, et al. Salmon calcitonin ameliorates migraine pain through modulation of CGRP release and dural mast cell degranulation in rats. Clin Exp Pharmacol Physiol 2018;45(6):536–546. 19. Theoharides TC, Kempuraj D, Sant GR. Mast cell involvement in interstitial cystitis: a review of human and experimental evidence. Urology. 2001;57(6 Suppl 1):47-55. 20. Moon TC, Befus AD, Kulka M. Mast cell mediators: their differential release and the secretory pathways involved. Front Immunol 2014;5:569. doi:10.3389/fimmu.2014.00569. 21. Krystel-Whittemore M, Dileepan KN, Wood JG. Mast Cell: A multi-functional master cell. Front Immunol 2016;6:620. 22. Tore F, Tuncel N. Mast cells: target and source of neuropeptides. Curr Pharm Des 2009;15(29):3433–3445. 23. Yu Y, Blokhuis BR, Garssen J, Redegeld FA. Non-IgE mediated mast cell activation. Eur J Pharmacol 2016;778:33-43. 24. Tore F, Tuncel N. Anatomical and functional relationships between sensory nerves and mast cells. Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 2011; 10: 10-17. https://doi.org/10.2174/187152311795325550. 25. Baun M, Pedersen MH, Olesen J, Jansen-Olesen I. Dural mast cell degranulation is a putative mechanism for headache induced by PACAP-38. Cephalalgia. 2012;32(4):337-45. 26. Jemima EA, Prema A, Thangam EB. Functional characterization of histamine H4 receptor on human mast cells. Mol Immunol 2014;62(1):19-28. 27. Juremalm M, Nilsson G. Chemokine receptor expression by mast cells. Chem Immunol Allergy 2005;87:130-44. 28. Theoharides TC. Neuroendocrinology of mast cells: Challenges and controversies. Exp Dermatol 2017;26(9):751-759. 29. Theoharides TC, Patra P, Boucher W, Letourneau R, Kempuraj D, Chiang G, Jeudy S, Hesse L, Athanasiou A. Chondroitin sulphate inhibits connective tissue mast cells. Br J Pharmacol 2000;131(6):1039-49. 30. Vliagoftis H, Mak L, Boucher W, Theoharides TC. Dual effect of spermine on mast cell secretion exhibits different calcium and temperature requirements. Int J Immunopharmacol 1999;21(9):547–559. 31. Vasiadi M, Kempuraj D, Boucher W, Kalogeromitros D, Theoharides TC. Progesterone inhibits mast cell secretion. Int J Immunopathol Pharmacol 2006;19(4):787-94. 32. Guhl S, Artuc M, Zuberbier T, Babina M. Testosterone exerts selective anti-inflammatory effects on human skin mast cells in a cell subset dependent manner. Exp Dermatol 2012;21(11):878-80. 33. Liu WL, Boulos PB, Lau HY, Pearce FL. Mast cells from human gastric mucosa: a comparative study with lung and colonic mast cells. Agents Actions. 1991;33(1-2):13-5. 34. Okayama Y, Church MK. Comparison of the modulatory effect of ketotifen, sodium cromoglycate, procaterol and salbutamol in human skin, lung and tonsil mast cells. Int Arch Allergy Immunol 1992;97(3):216-225. 35. Sugawara K, Zákány N, Hundt T, Emelianov V, Tsuruta D, Schäfer C, Kloepper JE, Bíró T, Paus R. Cannabinoid receptor 1 controls human mucosal-type mast cell degranulation and maturation in situ. J Allergy Clin Immunol 2013;132(1):182-193. 36. De Filippis D, Luongo L, Cipriano M, et al. Palmitoylethanolamide reduces granuloma-induced hyperalgesia by modulation of mast cell activation in rats. Mol Pain 2011;7:3. 37. Storms W, Kaliner MA. Cromolyn sodium: fitting an old friend into current asthma treatment. J Asthma. 2005;42(2):79-89. 38. Zhang T, Finn DF, Barlow JW, Walsh JJ. Mast cell stabilisers. Eur J Pharmacol. 2016;778:158-68. 39. Finn DF, Walsh JJ. Twenty-first century mast cell stabilizers. Br J Pharmacol 2013;170(1):23-37. 40. Malaviya R, Zhu D, Dibirdik I, Uckun FM. Targeting Janus kinase 3 in mast cells prevents immediate hypersensitivity reactions and anaphylaxis. J Biol Chem. 1999;274(38):27028-38. Erratum in: J Biol Chem 1999 Dec 31;274(53):38276. 41. Jensen BM, Beaven MA, Iwaki S, Metcalfe DD, Gilfillan AM. Concurrent inhibition of kit- and FcepsilonRI-mediated signaling: coordinated suppression of mast cell activation. J Pharmacol Exp Ther 2008;324(1):128-38. 42. Weston MC, Anderson N, Peachell PT. Effects of phosphodiesterase inhibitors on human lung mast cell and basophil function. Br J Pharmacol 1997;121(2):287-95. 43. Kilinc E, Tore F, Dagistan Y, Bugdayci G. Thymoquinone inhibits neurogenic inflammation underlying migraine through modulation of calcitonin gene-related peptide release and stabilization of meningeal mast cells in glyceryltrinitrate-induced migraine model in rats. Inflammation 2020;43(1):264–273. doi:10.1007/s10753-019-01115-w 44. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497–506. doi:10.1016/S0140-6736(20)30183-5 45. Zhang J, Shi GP. Mast cells and metabolic syndrome. Biochim Biophys Acta 2012;1822(1):14–20. 46. Kritas SK, Ronconi G, Caraffa A, Gallenga CE, Ross R, Conti P. Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy. J Biol Regul Homeost Agents. 2020;34(1):10.23812/20-Editorial-Kritas. doi:10.23812/20-Editorial-Kritas. 47. Conti P, Gallenga CE, Tetè G, et al. How to reduce the likelihood of coronavirus-19 (CoV-19 or SARS-CoV-2) infection and lung inflammation mediated by IL-1. J Biol Regul Homeost Agents 2020;34(2):10.23812/Editorial-Conti-2. doi:10.23812/Editorial-Conti-2 48. Conti P, Ronconi G, Caraffa A, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents 2020;34(2):1. doi:10.23812/CONTI-E 49. Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 2017;39(5):529–539. doi:10.1007/s00281-017-0629-x 50. Fu Y, Cheng Y, Wu Y. Understanding SARS-CoV-2-mediated inflammatory responses: from mechanisms to potential therapeutic tools. Virol Sin 2020;10.1007/s12250-020-00207-4. doi:10.1007/s12250-020-00207-4 51. Russell B, Moss C, George G, et al. Associations between immune-suppressive and stimulating drugs and novel COVID-19-a systematic review of current evidence. Ecancermedicalscience 2020;14:1022. 52. Ng PC, Lam CW, Li AM, et al. Inflammatory cytokine profile in children with severe acute respiratory syndrome. Pediatrics 2004;113(1 Pt 1):e7–e14. doi:10.1542/peds.113.1.e7 53. He L, Ding Y, Zhang Q, et al. Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS. J Pathol 2006;210(3):288–297. doi:10.1002/path.2067 54. Okabayashi T, Kariwa H, Yokota S, et al. Cytokine regulation in SARS coronavirus infection compared to other respiratory virus infections. J Med Virol 2006;78(4):417–424. doi:10.1002/jmv.20556 55. Bradding P. Mast cell regulation of airway smooth muscle function in asthma. Eur Respir J 2007;29(5):827–830. 56. Wang J, Wang BJ, Yang JC, et al. Advances in the research of mechanism of pulmonary fibrosis ınduced by corona virus disease 2019 and the corresponding therapeutic measures. Zhonghua Shao Shang Za Zhi 2020;36(0):E006. doi:10.3760/cma.j.cn501120-20200307-0013 57. Garbuzenko E, Berkman N, Puxeddu I, Kramer M, Nagler A, Levi-Schaffer F. Mast cells induce activation of human lung fibroblasts in vitro. Exp Lung Res 2004; 30:705-721. 58. Batlle M, Perez-Villa F, Lazaro A, et al. Correlation between mast cell density and myocardial fibrosis in congestive heart failure patients. Transplant Proc 2007; 39:2347-2349. 59. Ozbilgin MK, Inan S. The roles of transforming growth factor type beta3 (TGF-beta3) and mast cells in the pathogenesis of scleroderma. Clin Rheumatol 2003; 22:189-195. 60. Andersson CK, Mori M, Bjermer L, Lofdahl CG, Erjefalt JS. Alterations in lung mast cell populations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2010;181:206-217. 61. Balzar S, Chu HW, Strand M, Wenzel S. Relationship of small airway chymase-positive mast cells and lung function in severe asthma. Am J Respir Crit Care Med 2005; 171:431-439. 62. Hirata K, Sugama Y, Ikura Y, et al. Enhanced mast cell chymase expression in human idiopathic interstitial pneumonia. Int J Mol Med 2007; 19:565-570. 63. Andersson CK, Andersson-Sjöland A, Mori M, et al. Activated MCTC mast cells infiltrate diseased lung areas in cystic fibrosis and idiopathic pulmonary fibrosis. Respir Res. 2011;12(1):139.