Phagocyte population in the inflammatory pattern of the bronchi of asthma patients regulated by interleukin-17A and interferon-gamma during the airway response to a cold stimulus
https://doi.org/10.36604/1998-5029-2023-89-8-17
Abstract
Introduction. Based on the common effector functions of polymorphonuclear neutrophils and macrophages as phagocytic cells, their role in the formation of an acute reaction of the respiratory tract to a cold stimulus in patients with asthma is of concern.
Aim. The study of the concentration of phagocytes, IL-17A and IFN-γ in the inflammatory pattern of the bronchi of asthma patients depending on the airway reaction to a cold stimulus.
Materials and methods. 129 patients with asthma were examined. The design of the study included questioning patients using a validated questionnaire Asthma Control Test (ACT, Quality Metric Inc., 2002), collection of induced and spontaneously produced sputum, exhaled breath condensate (EBC), bronchoprovocation test with a 3-minute isocapnic hyperventilation with cold (-20ºС) air (IHCA) with an assessment of the airway response (ΔFEV1) by spirometry.
Results. Group 1 (n=55) included individuals with ΔFEV1 -10% and below, group 2 (n=74) – with ΔFEV1 above -10%: -15 (-21; -11) and -3.7 (-6.1; -0.38)%, respectively (p=0.0002). According to the level of ACT (17 [13; 21.5] and 19 [14; 22] points) and indicators of lung function (FEV1 [93.0±2.4 and 97.1±2.4%] and FEF25-75 [63.5±3.5 and 72.0±3.7%]), the patients had no significant intergroup differences. The pattern of bronchial inflammation in group 1 was mixed (neutrophils ≥40%), in group 2 – eosinophilic. In response to the IHCA test, the number of neutrophils significantly increased in the sputum of patients in group 1, the number of macrophages and the number of structurally intact epithelial cells decreased, in proportion to this, the level of IFN-γ and IFN-γ-inducible protein IP-10 (CXCL10) increased in the EBC in relation to patients of the 2nd group. A direct relationship was found between baseline concentrations of IP-10 and IFN-γ (Rs=0.7; p<0.01) in EBC.
Conclusion. The airway response to a cold stimulus of patients with asthma is accompanied by functional activation of phagocytic cells with an escalation of neutrophilic inflammation and a decrease in the number of macrophages infiltrating the bronchi associated with an increase in the concentration of IFN-γ, which stimulates the processes of respiratory burst and triggers cell destruction and cytolysis.
About the Authors
A. B. PirogovRussian Federation
Aleksey B. Pirogov, MD, PhD (Med.), Associate Professor, Senior Staff Scientist, Laboratory of Prophylaxis of Non-Specific Lung Diseases
22 Kalinina Str., Blagoveshchensk, 675000
A. G. Prikhodko
Russian Federation
Аnnа G. Prikhodko, MD, PhD, DSc (Med.), Main Staff Scientist, Laboratory of Functional Research of Respiratory System
22 Kalinina Str., Blagoveshchensk, 675000
D. E. Naumov
Russian Federation
Denis E. Naumov, PhD (Med.), Head of Laboratory of Molecular and Translational Research
22 Kalinina Str., Blagoveshchensk, 675000
J. M. Perelman
Russian Federation
Juliy M. Perelman, MD, PhD, DSc (Med.), Corresponding member of RAS, Рrofessor, Deputy Director on Scientific Work, Head of Laboratory of Functional Research of Respiratory System
22 Kalinina Str., Blagoveshchensk, 675000
References
1. Pirogov A.B., Kolosov V.P., Perel'man Y.M., Prikhodko A.G., Zinov'ev S.V., Gassan D.A., Mal'tseva T.A. [Airway inflammation patterns and clinical and functional features in patients with severe uncontrolled asthma and cold-induced airway hyperresponsiveness]. Pul'monologiya 2016; 26(6):701–707 (in Russian). https://doi.org/10.18093/086901892016266701707
2. Hastie A.T., Moore W.C., Meyers D.A., Vestal P.L., Li H., Peters S.P., Bleecker E.R. Analyses of asthma severity phenotypes and inflammatory proteins in subjects stratified by sputum granulocytes. J. Allergy Clin. Immunol. 2010; 125(5):1028–1036. https://doi.org/10.1016/j.jaci.2010.02.008
3. Wisam A.R., Pre´fontaine D., Chouiali F., Martin J.G., Olivenstein R., Lemie`re C., Hamid Q. TH17-associated cytokines (IL-17A and IL-17F) in severe asthma. J. Аllergy Сlin. Immunol. 2009; 123(5):1185–1187. https://doi.org/10.1016/j.jaci.2009.02.024
4. Kostareva O.S., Gabdulkhakov A.G., Kolyadenko I.A., Garber M.B., Tishchenko S.V. Interleukin-17: Functional and structural features, application as a therapeutic target. Biochemistry (Moscow) 2019; 84(Suppl.1):193–205. https://doi.org/10.1134/S0006297919140116
5. Krishnamoorthy N., Douda D.N., Brüggemann T. R., Ricklefs I., Duvall M.G., Abdulnour R.E., Martinod K., Tavares L., Wang X., Cernadas M., Israel E., Mauger D.Т., Bleecker E.R., Castro M., Erzurum S. C., Gaston B.M., Jarjour N.N., Wenzel S., Dunican E., Fahy J.V., Irimia D., Wagner D.D., Levy B.D. Neutrophil cytoplasts induce TH17 differentiation and skew inflammation toward neutrophilia in severe asthma. Sci. Immunol. 2018; 3(26):eaao4747. https://doi.org/10.1126/sciimmunol.aao4747
6. Duvall M.G., Krishnamoorthy N., Levy B.D. Non-type 2 inflammation in severe asthma is propelled by neutrophil cytoplasts and maintained by defective resolution. Allergol. Int. 2019; 68(2):143–149. https://doi.org/10.1016/j.alit.2018.11.006
7. Lindén А., Dahlén В. Interleukin-17 cytokine signalling in patients with asthma. Eur. Respir. J. 2014; 44(5):1319– 1331. https://doi.org/10.1183/09031936.00002314
8. Еsteban-Gorgojo I., Antolín-Amérigo D., Domínguez-Ortega J., Quirce S. Non-eosinophilic asthma: current perspectives. J. Asthma Allergy 2018; 11:267–281. https://doi.org/10.2147/JAA.S153097
9. Nikolskii A.A., Shilovskiy I.P., Yumashev K.V., Vishniakova L.I., Barvinskaia E.D., Kovchina V.I., Korneev A.V., Turenko V.N., Kaganova M.M., Brylina V.E., Nikonova A.A., Kozlov I.B., Kofi adi I.A., Sergeev I.V., Maerle A.V., Petukhova O.A., Kudlay D.A., Khaitov M.R. [Effect of local suppression of Stat3 gene expression in a mouse model of pulmonary neutrophilic inflammation]. Immunologiya 2021; 42 (6):600–614 (in Russian). https://doi.org/10.33029/0206-4952-2021-42-6-600-614
10. Schroder K., Hertzog P.J., Ravasi T., Hume D.A. Interferon-gamma: an overview of signals, mechanisms and functions. J. Leukoc. Biol. 2004; 75(2):163–189. https://doi.org/10.1189/jlb.0603252
11. Lutckii A.A., Zhirkov A.A., Lobzin D.Yu., Rao M., Alekseeva L.A., Maeurer M., Lobzin Yu.V. [Interferon-γ: biological function and application for study of cellular immune response]. Journal Infectology 2015; 7(4):10–22 (in Russian). https://www.elibrary.ru/vtodcz
12. Sarbaeva N.N., Ponomareva J.V., Milyakova M.N. [Macrophages: diversity of phenotypes and functions, interaction with foreign materials]. Genes & Cells 2016; 11(1):9–17 (in Russian). https://www.elibrary.ru/wclizl
13. Jiang Z., Zhu L. Update on the role of alternatively activated macrophages in asthma. J. Asthma Allergy 2016; 9:101‒107. https://doi.org/10.2147/JAA.S104508
14. Nikonova A.A., Khaitov M.R., Khaitov R.M. [Characteristics and role of macrophages in pathogenesis of acute and chronic lung diseases]. Medical Immunology (Russia) 2017; 19(6):657–672 (in Russian). https://doi.org/10.15789/1563-0625-2017-6-657-672
15. Arora S., Dev K., Agarwal B., Das P., Ali Syed M. Macrophages: their role, activation and polarization in pulmonary diseases. Immunobiology 2018; 223(4-5):383–396. https://doi.org/10.1016/j.imbio.2017.11.001
16. Malyshev I.Yu., Lyamina S.V., Shimshelashvili S.L., Vasserman E.N. [Functions of alveolar macrophages and surfactant protein D in lung disease]. Pulmonologiya 2011; (3):101‒107 (in Russian). https://doi.org/10.18093/0869-0189-2011-0-3-101-107
17. Lyamina S.V., Shimshelashvili S.L., Kalish S.V., Malysheva Е.V., Larionov N.P., Malyshev I.Yu. [Changes in phenotype and phenotypic flexibility of alveolar macrophages in inflammatory pulmonary diseases]. Pulmonologiya 2012; (6):83‒89 (in Russian). https://doi.org/10.18093/0869-0189-2012-0-6-83-89
18. Sheppard F.R., Kelher M.R., Moore E.E., McLaughlin N.J.D., Banerjee A., Silliman C.C. Structural or-ganization of the neutrophil NADPH oxidase: phosphorylation and translocation during priming and activation. J. Leukoc. Biol. 2005; 78(5):1025–1042. https://doi.org/10.1189/jlb.0804442
19. Savchenko A.A., Kudryavtsev I.V., Borisov A.G. [Methods of estimation and the role of respiratory burst in the pathogenesis of infectious and inflammatory diseases]. Russian Journal of Infection and Immunity 2017; 7(4):327–340 (in Russian). https://doi.org/10.15789/2220-7619-2017-4-327-340
20. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention (2023 update). Available at: www.ginasthma.org
21. Prikhodko A.G., Perelman J.M., Kolosov V.P. [Airway hyperresponsiveness]. Vladivostok: Dal'nauka; 2011 (in Russian). ISBN: 978-5-8044-1220-4.
22. Djukanovic R., Sterk P.J., Fahy J.V., Hargreave F.E. Standardised methodology of sputum induction and processing. Eur. Respir. J. 2002; 20(37):1s–2s. https://doi.org/10.1183/09031936.02.00000102
23. Perelman J.M., Naumov D.E., Prikhodko A.G., Kolosov V.P. [Mechanisms and manifestations of osmotic airway hyperresponsiveness]. Vladivostok: Dal'nauka; 2016 (in Russian). ISBN: 978-5-8044-1627-1.
24. Usui T., Preiss J.C., Kanno Y., Yao Z.J., Bream J.H., O'Shea J.J., Strober W. T-bet regulates Th1 responses through essential effects on GATA-3 function rather than on IFNG gene acetylation and transcription. J. Exp. Med. 2006; 203(3):755–766. https://doi.org/10.1084/jem.20052165
25. Panasenko O.M., Sergienko V.I. [Halogenizing stress and its biomarkers]. Vestn. Ross. Akad. Med. Nauk. 2010; (1):27‒39 (in Russian). PMID: 20408436.
26. Panasenko O.M., Gorudko I.V., Sokolov A.V. Hypochlorous acid as a precursor of free radicals in living systems. Biochemistry (Moscow) 2013; 78:1466–1489. https://doi.org/10.1134/S0006297913130075
27. Fujisawa T., Mann-Jong Chang M., Velichko S., Thai P., Hung Li-Y., Huang F., Phuong N., Chen Y., Wu R. NFκB mediates IL-1β– and IL-17A–induced MUC5B expression in airway epithelial cells. Am. J. Respir. Cell Mol. Biol. 2011; 45(2):246–252. https://doi.org/10.1165/rcmb.2009-0313OC
28. Chang Y., Al-Alwan L., Risse P.-A., Halayko A. J., Martin J.G., Baglole C. J., Eidelman D.H., Hamid Q. Th17-associated cytokines promote human airway smooth muscle cell proliferation. FASEB J. 2012; 26(12): 5152–5160. https://doi.org/10.1096/fj.12-208033
29. Schwandner R., Yamaguchi K., Caoa Z. Requirement of tumor necrosis factor receptor–associated factor (Traf)6 in interleukin 17 signal transduction. J. Exp. Med. 2000; 191(7):1233–1240. https://doi.org/10.1084/jem.191.7.1233
Review
For citations:
Pirogov A.B., Prikhodko A.G., Naumov D.E., Perelman J.M. Phagocyte population in the inflammatory pattern of the bronchi of asthma patients regulated by interleukin-17A and interferon-gamma during the airway response to a cold stimulus. Bulletin Physiology and Pathology of Respiration. 2023;(89):8-17. (In Russ.) https://doi.org/10.36604/1998-5029-2023-89-8-17