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Table of Contents
CLASSROOM READING - 1
Year : 2020  |  Volume : 6  |  Issue : 2  |  Page : 30-32

Host airway defense system


Professor, Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Date of Submission17-Aug-2020
Date of Acceptance19-Aug-2020
Date of Web Publication01-Sep-2020

Correspondence Address:
Dr. Anita Saxena
Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow - 226 014, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jrnm.jrnm_21_20

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How to cite this article:
Saxena A. Host airway defense system. J Renal Nutr Metab 2020;6:30-2

How to cite this URL:
Saxena A. Host airway defense system. J Renal Nutr Metab [serial online] 2020 [cited 2020 Sep 21];6:30-2. Available from: http://www.jrnm.in/text.asp?2020/6/2/30/294187



The respiratory tract is exposed to billions of particles and pathogens daily. Hippocrates was the first effort to epitomize the knowledge of respiration and lungs Viral infections constitute a class of viral diseases which have high mutation rates and high degree of dissimilarity between viruses' strains that hinder the development of broad-spectrum antiviral agents. Therefore, nature has provided human body a natural innate immune system which is designed to repel viral infections.[1] This classroom reading will identify the natural immune system's defense troops and their roles and look at simple ways to support it.

Mucus and mucins are the first line of natural defense in the host airway defense machinery. Its (mucus) fundamental importance is emphasized by its presence throughout the evolutionary pathways. Mucus is a mixture of water, ions, glycoproteins, proteins, and lipids.[2],[3],[4],[5] It plays a vital role in protecting the lungs from pathogens and toxins by forming the first line of innate defense in the respiratory tract.

Airway mucins are major components of the soluble layer and/or viscoelastic gel that comprises lung mucus in healthy airways and contributes to the mucociliary defense system that protects the lungs against pathogens and environmental toxins. Airway mucins are major components of the soluble layer and/or viscoelastic gel that comprise lung mucus in healthy airways and contribute to the mucociliary defense system that protects the lungs against pathogens and environmental toxins. Mucins are produced by epithelial tissues, and are classified into two groups (secreted and membrane bound), often performing inhibitory role. They are a family of high molecular weight, heavy glycoconjugates (glycosylated proteins) with repeat tandem domains rich in serine and threonine sites for O-glycosylation.[5],[6] These highly glycosylated proteins form a protective barrier and have a role in cell signaling by interaction with their specific receptors, the glycan-binding proteins (GBPs) on immune cells. The characteristic that attracts attention of mucins is their ability to form gel (gel-forming/secreted mucins at locus 11p15 [MUC2, MUC5AC, MUC5B, and MUC6]; membrane-bound mucins at locus 7q22, 3q, and 1q21 [MUC1, MUC3A, MUC3B, MUC4, MUC12, MUC13, and MUC17]);[6],[7],[8],[9],[10],[11],[12],[13],[14] therefore, they are a key component in most gel-like secretions, serving functions from lubrication to cell signaling to form chemical barriers. Mucins bind to pathogens as part of the immune system.

Ninety percent of the most prevalent secreted mucins are MUC5AC and MUC5B in the lungs, and only 10% are membrane-bound mucins (MUC1, MUC4, and MUC16). Recent studies utilizing RNA in situ hybridization and immunohistochemistry in normal lung show that although MUC5B is constitutively secreted throughout the conducting airway, except for the terminal bronchiole, the majority is produced in the distal airway by the secretory epithelial cells.[5],[6] MUC5AC is expressed predominantly in the proximal airway, its production being triggered by infection and cigarette smoke, as well as in allergic (type 2) inflammation.[1]

Viral infections trigger innate immune response to detect pathogen and their signaling to produce chemokines and cytokines, including type I interferon (IFN), to limit viral replication, and to spread to neighboring cells. To establish antiviral state, the Type I IFN released by infected cells binds to IFN receptor and triggers signaling pathways to induce expression of IFN-stimulated genes.

The selectins, consisting of E-, L-, and P-selectin, are a family of single-pass transmembrane cell adhesion proteins with an outer carbohydrate recognition domain that are widely expressed on endothelium, leukocytes, and platelets. The selectins play a key role in leucocyte trafficking out of the circulation and into the tissues. Selectin ligand expression on airway mucins is during inflammation, but what is much less clear is whether there are physiological selectin ligands expressed on mucins in the healthy lung that play a role in normal lung homeostasis.[6],[15],[16],[17]

Siglecs, GBPs of lectin family, are differentially expressed on restricted subsets of immune cells. The siglecs are immunomodulatory receptors and ligand engagement usually results in reduced inflammation though immune inhibitory sequences on cytoplasmic tails. Galectin (Gal)-1 has both pro- and anti-inflammatory features and has been shown to interact with MUC16. Gal-1 agonists are therapeutic targets as anti-inflammatories, but there are no clinical studies at the moment in chronic lung disease.

Threonine, an essential amino acid, which must be obtained from diet is found in the mucous membrane. Discovered in 1936 by William Cumming Rose, it is a constituent of Vitamin B-12. In humans, the gene for threonine dehydrogenase is an inactive pseudogene (nonfunctional segments of DNA that resemble functional genes). The amino acid gets its name from threonic acid (C4H8O5) because of its similarity in structure. A balanced protein-rich diet with fortified foods or supplements of Vitamin B-12 and selenium [18],[19],[20],[21] can maintain integrity of mucus defense system.[17],[18],[19],[20],[21],[22],[23],[24],[25],[26],[27]


  From Hippocrates' Wisdom Chest Top


Hippocrates [28] left a legacy for maintaining human body in shape with nature's gifts. His medicine was humble and passive. He believed in “the healing power of nature” Vis_medicatrix_naturae”vis medicatrix naturae” in Latin. Of dozens of simple ways advised by Hippocrates on how to keep immune systems vibrant and enhance innate energy here are a few lessons which can be followed during SARS-2 COV-2 Pandemic. Hippocrates insisted on importance of diet, exercise, and thought in the maintenance of health.[23],[24],[25],[26],[27] Imbalance and stress in any of these areas weakens the immune system.

  1. Devour oxygen. Modernization has disconnect us from the natural world, depriving us from positive influence of nature. Surround yourself with nature to connect with self. Stay in or near oxygen-rich environments like running streams, greenhouses (you can create one at home) and learn to breathe deeply without exerting yourself. Eat plenty of raw, oxygen-rich green foods. Use safe oxygen products in drinking water. In view of pandemic which makes it necessary to remain indoors for most of the day, use an oxygen-producing air purifier in home and at place of work.
  2. Drink pure distilled water and keep yourself well hydrated. Body weight, body surface area, and other related factors influence the water requirements of an individual. Adults should consume 40 mL of water per kilogramme of body weight (keeping in mind country of residence and season)[29],[30],[31].
  3. Prefer vegetarian food and of which 75% (or higher) should be raw like sprouts and green vegetables which provide most balanced and nourishing diet.
  4. Drink freshly-made sprout/vegetable green drinks.
  5. Use blue-green algae daily. Blue-green algae has high amounts of protein, iron, and other minerals and has beneficial effects on the immune system, inflammation, and against viral infections. Individuals
  6. Avoid using foods and condiments that contain immune-suppressing ingredients (prefer low antigen content (LAC) diet), like salt, refined sugars and flours, dairy products, vinegars, heated oils, food preservatives and colourings.
  7. How safe are you with microwave cooking?
  8. Include moderate exercise (20-30 minutes) in daily routine. Exercise will preserve lean mass in those confined at homes.
  9. Detoxify your immune system once a week. Switch over to freshly-made juices and water
  10. A positive attitude improves mental and physical health. Try it.


Keep your defense system healthy. Keep smiling.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest



 
  References Top

1.
Castelli J, Wood KA, Youle RJ. The 2-5A system in viral infection and apoptosis. Biomed Pharmacother 1998;52:386-90.  Back to cited text no. 1
    
2.
Thornton DJ, Sheehan JK. From mucins to mucus: Toward a more coherent understanding of this essential barrier. Proc Am Thorac Soc 2004;1:54-61.  Back to cited text no. 2
    
3.
Linden SK, Sutton P, Karlsson NG, Korolik V, McGuckin MA. Mucins in the mucosal barrier to infection. Mucosal Immunol 2008;1:183-97.  Back to cited text no. 3
    
4.
Lai SK, Wang YY, Hida K, Cone R, Hanes J. Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses. Proc Natl Acad Sci U S A 2010;107:598-603.  Back to cited text no. 4
    
5.
Denneny E, Sahota J, Beatson R, Thornton D, Burchell J, Porter J. Mucins and their receptors in chronic lung disease. Clin Transl Immunology 2020;9:e01120.  Back to cited text no. 5
    
6.
He L, Feng QQ, Zhang Q, Zhang B, Wu SS, Gong JH. Protective role of overexpressed MUC5AC against fibrosis in MHV-68-induced combined pulmonary fibrosis and emphysema mouse model. J Med Virol 2020 1-10:10.1002/jmv.26326.doi: 10.1002/jmv.26326 [Epub ahead of print].  Back to cited text no. 6
    
7.
Koeppen M, McNamee EN, Brodsky KS, Aherne CM, Faigle M, Downey GP, et al. Detrimental role of the airway mucin Muc5ac during ventilator-induced lung injury. Mucosal Immunol 2013;6:762-75.  Back to cited text no. 7
    
8.
Roy MG, Livraghi-Butrico A, Fletcher AA, McElwee MM, Evans SE, Boerner RM, et al. Muc5b is required for airway defence. Nature 2014;505:412-6.  Back to cited text no. 8
    
9.
Morcillo EJ, Cortijo J. Mucus and MUC in asthma. Curr Opin Pulm Med 2006;12:1-6.  Back to cited text no. 9
    
10.
Rogers DF. Physiology of airway mucus secretion and pathophysiology of hypersecretion. Respir Care 2007;52:1134-46.  Back to cited text no. 10
    
11.
Liu Y, Di YP. Effects of second hand smoke on airway secretion and mucociliary clearance. Front Physiol 2012;3:342.  Back to cited text no. 11
    
12.
Rose MC, Voynow JA. Respiratory tract mucin genes and mucin glycoproteins in health and disease. Physiol Rev 2006;86:245-78.  Back to cited text no. 12
    
13.
Cagnoni AJ, Pérez Sáez JM, Rabinovich GA, Mariño KV. Turning-off signaling by siglecs, selectins, and galectins: Chemical inhibition of glycan-dependent interactions in cancer. Front Oncol 2016;6:109.  Back to cited text no. 13
    
14.
Zhu Z, Homer RJ, Wang Z, Chen Q, Geba GP, Wang J, et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest 1999;103:779-88.  Back to cited text no. 14
    
15.
Jakubzick C, Choi ES, Kunkel SL, Evanoff H, Martinez FJ, Puri RK, et al. Augmented pulmonary IL-4 and IL-13 receptor subunit expression in idiopathic interstitial pneumonia. J Clin Pathol 2004;57:477-86.  Back to cited text no. 15
    
16.
Lieleg O, Lieleg C, Bloom J, Buck CB, Ribbeck K. Mucin biopolymers as broad-spectrum antiviral agents. Biomacromolecules 2012;13:1724-32.  Back to cited text no. 16
    
17.
Oliver Lieleg, Corinna Lieleg, Jesse Bloom, Christopher B. Buck, Katharina Ribbeck. Mucin biopolymers as broad-spectrum antiviral agents Biomacromolecules. 2012; 13:1724-32.  Back to cited text no. 17
    
18.
Zhi-xue Cheng, Chang Guo, Zhuang-gui Chen, Tian-ci Yang, Jian-ying Zhang, Jie Wang, Jia-xin Zhu, Dan Li, Tian-tuo Zhang, Hui Li, Bo Pengand Xuan-xian Peng Glycine, serine and threonine metabolism confounds efficacy of complement-mediated killing Nat Commun. 2019;10:3325.  Back to cited text no. 18
    
19.
“Nomenclature and Symbolism for Amino Acids and Peptides”. IUPAC-IUB Joint Commission on Biochemical Nomenclature. 1983. Archived from the original on 9 October 2008. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1153490. [Last Retrieved 2018 Mar 05].  Back to cited text no. 19
    
20.
Carter, Herbert E.; West, Harold D. (1940). “dl-Threonine”. Organic Syntheses. 20:101.; Collective Volume, 3, p. 813.  Back to cited text no. 20
    
21.
Raïs, Badr; Chassagnole, Christophe; Lettelier, Thierry; Fell, David; Mazat, Jean-Pierre. “Threonine synthesis from aspartate in Escherichia coli cell-free extracts: pathway dynamics”. J Biochem. 2001;356:425–32.  Back to cited text no. 21
    
22.
I Jaspers, W Zhang, L E Brighton, J L Carson, M Styblo, M A Beck Selenium deficiency alters epithelial cell morphology and responses to influenza Free Radic Biol Med 2007;42:1826-37.  Back to cited text no. 22
    
23.
Stipanuk, Martha H.; Caudill, Marie A. (2013-08-13). Biochemical, Physiological, and Molecular Aspects of Human Nutrition - E-Book. Elsevier Health Sciences. ISBN 9780323266956.  Back to cited text no. 23
    
24.
Di Renzo L, Gualtieri P, Romano L, Marrone G, Noce A, Pujia A, et al. Role of personalized nutrition in chronic-degenerative diseases. Nutrients. 2019;11:1707. doi: 10.3390/nu11081707.  Back to cited text no. 24
    
25.
De Lorenzo A, Bernardini S, Gualtieri P, Cabibbo A, Perrone MA, Giambini I, et al. Mediterranean meal versus Western meal effects on postprandial ox-LDL, oxidative and inflammatory gene expression in healthy subjects: a randomized controlled trial for nutrigenomic approach in cardiometabolic risk. Acta Diabetol. 2017;54:141-9. doi: 10.1007/s00592-016-0917-2.  Back to cited text no. 25
    
26.
Soldati L, Di Renzo L, Jirillo E, Ascierto PA, Marincola FM, De Lorenzo A. The influence of diet on anti-cancer immune responsiveness. J Transl Med. 2018;16:75. doi: 10.1186/s12967-018-1448-0.  Back to cited text no. 26
    
27.
Di Renzo L, Gualtieri P, Pivari F, Soldati L, Attinà A, Cinelli G, et al. Eating habits and lifestyle changes during COVID-19 lockdown: an Italian survey. Journal of translational medicine, 2020;18:229-5.  Back to cited text no. 27
    
28.
Lindsay Johnson Our Immune System: A Miracle of Creation in Hippocrates Jun 2012;12.  Back to cited text no. 28
    
29.
Advances and gaps in recommendations for adequate water intake in China Na Zhang, Songming Du, Yuexin Yang, Guansheng Asia Pac J Clin Nutr 2019;28:665-74.  Back to cited text no. 29
    
30.
Joan Gandy Water intake: validity of population assessment and recommendations Eur J Nutr. 2015;54(Suppl 2):11-16.  Back to cited text no. 30
    
31.
Natsume O, Kaneko Y, Hirayama A, Fujimoto K, Hirao Y. Fluid control in elderly patients with nocturia. Int J Urol. 2010;16:307-13.  Back to cited text no. 31
    




 

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