Atmospheric Reactive Oxygen Species and Some Aspects of the Antiviral Protection at the Respiratory Epithelium

Abstract

The review summarizes literature data on molecular and biochemical mechanisms of nonspecific protection of respiratory epithelium. The special attention is paid to comprehensive analysis of up-to-date data on the activity of the lactoperoxidase system expressed on the surface of the respiratory epithelium which provides the generation of hypothiocyanate and hypoiodite in the presence of locally produced or inhaled hydrogen peroxide. Molecular mechanisms of production of active compounds with antiviral and antibacterial effects, expression profiles of enzymes, transporters and ion channels involved in the generation of hypothiocyanite and hypoiodite in the mucous membrane of the respiratory system in physiological and pathological conditions (inflammation) are discussed. A hypothesis about the effect of atmospheric air composition on the efficiency of hypothiocyanate and hypoiodite generation in the respiratory epithelium in the context of its antibacterial and antiviral protection is presented. The causes and consequences of insufficiency of the lactoperoxidase system caused by the action of atmospheric factors are discussed in the context of controlling the sensitivity of the epithelium to the action of bacterial agents and viruses. Good evidence exists that restoration of the lactoperoxidase system activity can be achieved by application of pharmacological agents aimed to compensate for the deficit of halides in tissues, and by the control of chemical composition of the inhaled air.

Keywords: hypoiodite; hypothiocyanite; lactoperoxidase; reactive nitrogen species; reactive oxygen species; respiratory epithelium.

Fig. 1.

Key mechanisms of activation of epithelial cells of the respiratory tract mucosa during bacterial and viral infections, associated with cytokine-mediated induction of the activity of NADPH oxidases (NOX/DUOX), lactoperoxidase (LPO) and substrate transporters of reactions catalyzed by them (anoctamin 1 Ano1, sodium iodide symporter NIS, pendrin), production of the superoxide radical anion O, hydrogen peroxide and its derivatives (hypothiocyanate HOSCN, hypoiodite HOI).

Fig. 2.

Formation and conversion of intracellular and extracellular pools of hydrogen peroxide, providing production of hypothiocyanate and hypoiodite on the surface of epithelial cells of the respiratory tract mucosa. SOD, superoxide dismutase; LPO, lactoperoxidase; NIS, sodium iodide symporter.

Fig. 3.

Transport and enzymatic systems of bronchial tree epithelial cells that form lactoperoxidase-dependent nonspecific defense mechanisms.

Fig. 4.

Production of thiocyanate derivatives by peroxidases causing modification of cellular proteins and a change in the ratio of reduced and oxidized pyridine nucleotides. LPO—lactoperoxidase, MPO—myeloperoxidase, EPO—eosinophilic peroxidase.

Fig. 5.

Probable mechanism of the anti-inflammatory action of hypothiocyanate OSCNˉ, associated with suppression of the activity of glycolytic and the pentose phosphate pathway enzymes (GAPDv—glyceraldehyde-3-phosphate dehydrogenase, HK—hexokinase, G6PD—glucose-6-phosphate dehydrogenase, aldolase) and M1-polarization of tissue macrophages.