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Insights Gained Into the Treatment of COVID19 by Pulmonary Surfactant and Its Components.

ABSTRACT: Pulmonary surfactant constitutes an important barrier that pathogens must cross to gain access to the rest of the organism via the respiratory surface. The presence of pulmonary surfactant prevents the dissemination of pathogens, modulates immune responses, and optimizes lung biophysical activity. Thus, the application of pulmonary surfactant for the treatment of respiratory diseases provides an effective strategy. Currently, several clinical trials are investigating the use of surfactant preparations to treat patients with coronavirus disease 2019 (COVID-19). Some factors have been considered in the application of pulmonary surfactant for the treatment COVID-19, such as mechanical ventilation strategy, timing of treatment, dose delivered, method of delivery, and preparation utilized. This review supplements this list with two additional factors: accurate measurement of surfactants in patients and proper selection of pulmonary surfactant components. This review provides a reference for ongoing exogenous surfactant trials involving patients with COVID-19 and provides insight for the development of surfactant preparations for the treatment of viral respiratory infections.

SUBMITTER: Li D

PROVIDER: S-EPMC9110697 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Insights Gained Into the Treatment of COVID19 by Pulmonary Surfactant and Its Components.

Li Dan D Wang Xianzheng X Liao Yingzhao Y Wang Shouchuan S Shan Jinjun J Ji Jianjian J

Frontiers in immunology 20220503

Pulmonary surfactant constitutes an important barrier that pathogens must cross to gain access to the rest of the organism <i>via</i> the respiratory surface. The presence of pulmonary surfactant prevents the dissemination of pathogens, modulates immune responses, and optimizes lung biophysical activity. Thus, the application of pulmonary surfactant for the treatment of respiratory diseases provides an effective strategy. Currently, several clinical trials are investigating the use of surfactant ...[more]

PMID: 35592339

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Project description:Rhinoviruses (RVs) are major instigators of acute exacerbations of asthma, COPD and other respiratory diseases. RVs are categorized into three species (RV-A, RV-B, and RV-C), which comprise more than 160 serotypes, making it difficult to develop an effective vaccine. Currently no effective treatment for RV infection is available. Pulmonary surfactant is an extracellular complex of lipids and proteins that plays a central role in regulating innate immunity in the lung. The minor pulmonary surfactant lipids, palmitoyl-oleoyl-phosphatidylglycerol (POPG) and phosphatidylinositol (PI), are potent regulators of inflammatory processes, and exert antiviral activity against respiratory syncytial virus (RSV) and influenza A viruses (IAV). In the current study, we examined the potencies of POPG and PI against rhinovirus A16 (RV-A16) in primary human airway epithelial cells (AECs) differentiated at an air-liquid interface (ALI). After AECs were infected with RV-A16, PI reduced viral RNA copy number by 80% and downregulated (55-65%) expression of antiviral genes (MDA5, IRF7 and IFN-lambda). In contrast, POPG only slightly decreased MDA5 (24%) and IRF7 (11%) gene expression but did not inhibit IFN-lambda gene expression or RV-A16 replication in AECs. However, both POPG and PI inhibited (50-80%) IL6 and CXCL11 gene expression and protein secretion. PI treatment dramatically attenuated global gene expression changes induced by RV-A16 infection in AECs. Cell type enrichment analysis of viral regulated genes opposed by PI treatment revealed that PI inhibited viral induction of goblet cell metaplasia and virus-induced downregulation of ciliated, club, and ionocyte cell types. Notably, PI treament altered the ability of RV-A16 to regulate expression of some phosphatidylinositol 4-kinase (PI4K), acyl-CoA binding domain containing (ACBD) and low density lipoprotein receptor (LDLR) genes that play critical roles in the formation and functioning of replication organelles (ROs) required for RV replication in host cells. These data suggest PI can be used as a potent, non-toxic antiviral agent for RV infection prophylaxis and treatment.

Project description:Exposure of lung to hypoxia has been previously reported to be associated with significant alterations in the protein content of bronchoalveolar lavage (BAL) and lung tissue. In the present work we have used a proteomic approach to describe the changes in protein complement induced by moderate long-term hypoxia (rats exposed to 10% O2 for 72h) in BAL and lung tissue, with a special focus on the proteins associated with pulmonary surfactant, which could indicate adaptation of this system to limited oxygen availability. The analysis of the general proteomic profile indicates a hypoxia-induced increase in proteins associated with inflammation both in lavage and lung tissue. Analysis at mRNA and protein levels revealed no significant changes induced by hypoxia on the content in surfactant proteins or their apparent oligomeric state. In contrast, we detected a hypoxia-induced significant increase in the expression and accumulation of hemoglobin in lung tissue, at both mRNA and protein levels, as well as an accumulation of hemoglobin both in BAL and associated with surface-active membranes of the pulmonary surfactant complex. Evaluation of pulmonary surfactant surface activity from hypoxic rats showed no alterations in its spreading ability, ruling out inhibition by increased levels of serum or inflammatory proteins.Biological significanceThis work reveals that hypoxia induces extensive changes in the proteomic profile of lung bronchoalveolar lavage, including the presence of proteins related with inflammation both in lung tissue and lavage, and a significant increase in the synthesis and secretion by the lung tissue of different forms of hemoglobin. The level of specific pulmonary surfactant-associated proteins is not substantially altered due to hypoxia, but hypoxia-adapted surfactant exhibits an enhanced ability to form surface-active films at the air-liquid interface. The increased amount of β-globin integrated into the operative surfactant complexes obtained from hypoxic rats is a relevant feature that points to the existence of adaptive responses coupling surfactant function and oxygen availability.

Dataset Information

Insights Gained Into the Treatment of COVID19 by Pulmonary Surfactant and Its Components.

Publications

Insights Gained Into the Treatment of COVID19 by Pulmonary Surfactant and Its Components.

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