Protective mechanisms of lungs

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Respiratory system maintains a close contact with the environment and is constantly exposed to numerous pathogenic factors. In response to action of pathogen, different strategies of specific and non-specific defense have been formed: barrier functions of the epithelium, defense reflexes (coughing, sneezing), muco-ciliary clearance, resident and recruited cells, secretion of a number of proteins and peptides with protective functions.

Aim. To systematize modern concepts of the protective mechanisms of lungs on the basis of the data of the relevant literature.

In the work, the mechanisms and clinical significance of muco-ciliary clearance, resident alveolar and recruited macrophages, epithelial cells, neutrophils, lymphocytes and platelets are analyzed.

Conclusion. The presented mechanisms can counteract the action of various pathogenic agents with sufficient effectiveness. However, in some cases an organism develops insufficient, excessive or perverted response to permeation of pathogens. This results in damage to the lung tissue by exogenous agents and/or by self immune system. Knowledge of protective mechanisms realized in the respiratory system, is necessary for understanding pathogenesis of respiratory diseases and for choice of the optimal treatment tactics.

Full Text

Restricted Access

About the authors

Svetlana A. Shustova

Ryazan State Medical University

Email: sv_shustova@mail.ru
ORCID iD: 0000-0002-5528-6742
SPIN-code: 8866-5935
ResearcherId: AAG-5064-2020

MD, PhD, Associate Professor of the Department of Pathophysiology

Russian Federation, Ryazan

Tatiana A. Miroshkina

Ryazan State Medical University

Author for correspondence.
Email: mirta62@yandex.ru
ORCID iD: 0000-0002-9179-5181
SPIN-code: 2779-0313
ResearcherId: AAG-5068-2020

MD, PhD, Associate Professor of the
Department of Pathophysiology

Russian Federation, Ryazan

References

  1. Moroz VV, Tuchina LM, Poroshenko GG. Mechanisms of Protection of the Lung. Obshchaya Reanimatologiya. 2005;1(5):69-77. (In Russ).
  2. Asgharian B, Price OT, Oldham M, et al. Computational modeling of nanoscale and microscale particle deposition, retention and dosimetry in the mouse respiratory tract. Inhalation Toxicology. 2014;26 (14):829-42. doi: 10.3109/08958378.2014.935535
  3. Widdicombe JH, Wine JJ. Airway Gland Structure and Function. Physiological Reviews. 2015;95(4):1241-319. doi: 10.1152/physrev.00039.2014
  4. Whitsett JA, Alenghat T. Respiratory epithelial cells orchestrate pulmonary innate immunity. Nature Immunology. 2015;16(1):27-35. doi: 10.1038/ni.3045
  5. Whitsett JA. Airway Epithelial Differentiation and Mucociliary Clearance. Annals of the American Thoracic Society. 2018;15(Suppl 3):S143-8. doi: 10.1513/AnnalsATS.201802-128AW
  6. Ma J, Rubin BK, Voynow JA. Mucins, Mucus, and Goblet Cells. Chest. 2018;154(1):169-76. doi:10. 1016/j.chest.2017.11.008
  7. Bonser LR, Erle DJ. Airway Mucus and Asthma: The Role of MUC5AC and MUC5B. Journal of Clinical Medicine. 2017;6(12):112. doi: 10.3390/jcm6120112
  8. Roy MG, Livraghi-Butrico A, Fletcher AA, et al. Muc5b is required for airway defence. Nature. 2014;505(7483):412-6. doi: 10.1038/nature12807
  9. Evans CM, Raclawska DS, Ttofali F, et al. The polymeric mucin Muc5ac is required for allergic airway hyperreactivity. Nature Communications. 2015;6:(6281). doi: 10.1038/ncomms7281
  10. Iida H, Matsuura S, Shirakami G, et al. Differential effects of intravenous anesthetics on ciliary motility in cultured rat tracheal epithelial cells. Canadian Journal of Anesthesia. 2006;53(3):242-9. doi: 10.1007/bf03022209
  11. Shapiro AJ, Zariwala MA, Ferkol T, et al. Diagnosis, monitoring, and treatment of primary ciliary dyskinesia: PCD foundation consensus recommendations based on state of the art review. Pediatric Pulmonology. 2016;51(2):115-32. doi: 10.1002/ppul.23304
  12. Zhou-Suckow Z, Duerr J, Hagner M, et al. Airway mucus, inflammation and remodeling: emerging links in the pathogenesis of chronic lung diseases. Cell and Tissue Research. 2017;367(3):537-50. doi: 10.1007/s00441-016-2562-z
  13. Guschin MY, Barkhina TG, Golovanova VE, et al. Modern views on the relationship of the upper and lower respiratory tract in allergic rhinitis and asthma. I.P. Pavlov Russian Medical Biological Herald. 2011;(4):154-60. (In Russ).
  14. Murphy J, Summer R, Wilson AA, et al. The Prolonged Life-Span of Alveolar Macrophages. American Journal of Respiratory Cell and Molecular Biology. 2008;38(4):380-5. doi: 10.1165/rcmb.2007-0224RC
  15. Taylor PR, Martinez-Pomares L, Stacey M, et al. Macrophage receptors and immune recognition. Annual Review of Immunology. 2005;23:901-44. doi: 10.1146/annurev.immunol.23.021704.115816
  16. Gregory AD, Hogue LA, Ferkol TW, et al. Regulation of systemic and local neutrophil responses by G-CSF during pulmonary Pseudomonas aeruginosa infection. Blood. 2006;109(8):3235-43. doi: 10.1182/blood-2005-01-015081
  17. Pittet LA, Quinton LJ, Yamamoto K, et al. Earliest Innate Immune Responses Require Macrophage RelA during Pneumococcal Pneumonia. American Journal of Respiratory Cell and Molecular Biology. 2011;45(3):573-81. doi: 10.1165/rcmb.2010-0210OC
  18. Han S, Mallampalli RK. The Role of Surfactant in Lung Disease and Host Defense against Pulmonary Infections. Annals of the American Thoracic Society. 2015;12(5):765-74. doi: 10.1513/AnnalsATS.201411-507FR
  19. Kamata H, Yamamoto K, Wasserman GA, et al. Epithelial Cell – Derived Secreted and Transmembrane 1a Signals to Activated Neutrophils during Pneumococcal Pneumonia. American Journal of Respiratory Cell and Molecular Biology. 2016; 55(3):407-18. doi: 10.1165/rcmb.2015-0261OC
  20. Jones MR, Simms BT, Lupa MM, et al. Lung NF-κB Activation and Neutrophil Recruitment Require IL-1 and TNF Receptor Signaling during Pneumococcal Pneumonia. Journal of Immunology. 2005; 175(11):7530-5. doi: 10.4049/jimmunol.175.11.7530
  21. Paats MS, Bergen IM, Hanselaar WEJJ, et al. T helper 17 cells are involved in the local and systemic inflammatory response in community-acquired pneumonia. Thorax. 2013;68(5):468-74. doi: 10.1136/thoraxjnl-2012-202168
  22. Chan YR, Liu JS, Pociask DA, et al. Lipocalin 2 is required for pulmonary host defense against Klebsiella infection. Journal of Immunology. 2009; 182(8):4947-56. doi: 10.4049/jimmunol.0803282
  23. Choi S-M, Mc Aleer JP, Zheng M, et al. Innate Stat3-mediated induction of the antimicrobial protein Reg3γ is required for host defense against MRSA pneumonia. The Journal of Experimental Medicine. 2013;210(3):551-61. doi: 10.1084/jem.20120260
  24. Traber KE, Hilliard KL, Allen E, et al. Induction of STAT3-Dependent CXCL5 Expression and Neutrophil Recruitment by Oncostatin-M during Pneumonia. American Journal of Respiratory Cell and Molecular Biology. 2015;53(4):479-88. doi:10.1165/ rcmb.2014-0342OC
  25. Yamamoto K, Ahyi A-NN, Pepper-Cunningham ZA, et al. Roles of Lung Epithelium in Neutrophil Recruitment During Pneumococcal Pneumonia. American Journal of Respiratory Cell and Molecular Biology. 2014;50(2):253-62. doi: 10.1165/rcmb.2013-0114OC
  26. Evans SE, Scott BL, Clement CG, et al. Stimulated innate resistance of lung epithelium protects mice broadly against bacteria and fungi. American Journal of Respiratory Cell and Molecular Biology. 2010;42(1):40-50. doi: 10.1165/rcmb.2008-0260OC
  27. Craig A, Mai J, Cai S, et al. Neutrophil recruitment to the lungs during bacterial pneumonia. Infection and Immunity. 2009;77(2):568-75. doi: 10.1128/iai.00832-08
  28. Brinkmann V. Neutrophil Extracellular Traps in the Second Decade. Journal of Innate Immunity. 2018; 10(5-6):414-21. doi: 10.1159/000489829
  29. Maus U, von Grote K, Kuziel WA, et al. The role of CC chemokine receptor 2 in alveolar monocyte and neutrophil immigration in intact mice. American Journal of Respiratory and Critical Care Medicine. 2002;166(3):268-73. doi: 10.1164/rccm.2112012
  30. Aggarwal NR, King LS, D’Alessio FR. Diverse macrophage populations mediate acute lung inflammation and resolution. American Journal of Physiology, Lung Cellular and Molecular Physiology. 2014; 306(8):L709-25. doi: 10.1152/ajplung.00341.2013
  31. Belskikh E.S., Uryas'ev O.M., Zvyagina V.I., et al. Investigation of oxidative stress and function of mitochondria in mononuclear leukocytes of blood in patients with chronic bronchitis and with chronic obstructive pulmonary disease. Nauka Molodykh (Eruditio Juvenium). 2018;6(2):203-10. (In Russ).
  32. Sonnenberg GF, Artis D. Innate lymphoid cells in the initiation, regulation and resolution of inflammation. Nature Medicine. 2015;21(7):698-708. doi: 10.1038/nm.3892
  33. Orange JS. Human natural killer cell deficiencies and susceptibility to infection. Microbes and Infection. 2002;4(15):1545-58. doi: 10.1016/s1286-4579(02)00038-2
  34. Abboud G, Tahiliani V, Desai P, et al. Natural Killer Cells and Innate Interferon Gamma Participate in the Host Defense against Respiratory Vaccinia Virus Infection. Journal of Virology. 2015;90(1): 129-41. doi: 10.1128/jvi.01894-15
  35. Elhaik-Goldman S, Kafka D, Yossef R, et al. The natural cytotoxicity receptor 1 contribution to early clearance of streptococcus pneumoniae and to natural killer-macrophage cross talk. PLoS One. 2011; 6(8):e23472. doi: 10.1371/journal.pone.0023472
  36. Minutti CM, Jackson-Jones LH, García-Fojeda B, et al. Local amplifiers of IL-4Rα–mediated macrophage activation promote repair in lung and liver. Science. 2017;356(6342):1076-80. doi: 10.1126/science.aaj2067
  37. Muir R, Osbourn M, Dubois AV, et al. Innate Lymphoid Cells Are the Predominant Source of IL-17A during the Early Pathogenesis of Acute Respiratory Distress Syndrome. American Journal of Respiratory and Critical Care Medicine. 2016;193 (4):407-16. doi: 10.1164/rccm.201410-1782OC
  38. Nakasone C, Yamamoto N, Nakamatsu M, et al. Accumulation of gamma/delta T cells in the lungs and their roles in neutrophil-mediated host defense against pneumococcal infection. Microbes and
  39. Infection. 2007;9(3):251-8. doi: 10.1016/j.micinf.2006.11.015
  40. Baumgarth N. The double life of a B-1 cell: self-reactivity selects for protective effector functions. Nature Reviews. Immunology. 2011;11(1):34-46. doi: 10.1038/nri2901
  41. Yadav H, Kor DJ. Platelets in the pathogenesis of acute respiratory distress syndrome. American Journal of Physiology, Lung Cellular and Molecular Physiology. 2015;309(9):L915-23. doi: 10.1152/ajplung.00266.2015
  42. De Stoppelaar SF, van’t Veer C, Roelofs JJTH, et al. Platelet and endothelial cell P-selectin are required for host defense against Klebsiella pneumoniae-induced pneumosepsis. Journal of Thrombosis and Haemostasis. 2015;13(6):1128-38. doi: 10.1111/jth.12893
  43. Krijgsveld J, Zaat SAJ, Meeldijk J, et al. Thrombocidins, Microbicidal Proteins from Human Blood Platelets, Are C-terminal Deletion Products of CXC Chemokines. The Journal of Biological Chemistry. 2000; 275(27):20374-81. doi: 10.1074/jbc.275.27.20374
  44. Lê VB, Schneider JG, Boergeling Y, et al. Platelet Activation and Aggregation Promote Lung Inflammation and Influenza Virus Pathogenesis. American Journal of Respiratory and Critical Care Medicine. 2015;191(7):804-19. doi: 10.1164/rccm.201406-1031OC

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2021 Eco-Vector


Media Registry Entry of the Federal Service for Supervision of Communications, Information Technology and Mass Communications (Roskomnadzor) PI No. FS77-76803 dated September 24, 2019.



This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies