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MEDICC Review Oct 2022In inflammatory respiratory diseases, the imbalance between proteases and endogenous protease inhibitors leads to an exacerbated activity of human neutrophil elastase (a...
INTRODUCTION
In inflammatory respiratory diseases, the imbalance between proteases and endogenous protease inhibitors leads to an exacerbated activity of human neutrophil elastase (a protease that destroys the extracellular matrix and stimulates proinflammatory cytokine release). Elastase is considered a target in the search for therapeutic treatments for inflammatory respiratory diseases. Pulmonary surfactant is a promising product for this purpose, because in addition to its biophysical function, it has anti-inflammatory properties.
OBJECTIVE
Evaluate effect of the Cuban porcine pulmonary surfactant (Surfacen), the rCmPI-II elastase inhibitor, and the Surfacen/rCmPI-II combination on activated neutrophil elastase activity in vitro, and determine if Surfacen's interface property changes in the presence of the inhibitor.
METHODS
The anti-elastase effect of Surfacen, rCmPI-II and the Surfacen/rCmPI-II combination was evaluated in an in vitro model of activated neutrophils, previously purified from the blood of healthy subjects. The cells were stimulated with LPS/fMLP and were incubated with different concentrations of Surfacen, rCmPI-II and the Surfacen/rCmPI-II combination. Elastase activity was measured. The interface property was determined on a Langmuir surface balance. The new index, called the abdominal adipose deposit index, was obtained by multiplying the subcutaneous fat thickness by visceral fat thickness, both measured by ultrasound. A cutoff point was established that facilitated discernment of an unhealthy phenotype: normal weight but metabolically obese, a cardiometabolic risk factor.
RESULTS
Surfacen at 10 mg/mL inhibited 71% of stimulated neutrophil elastase activity. rCmPI-II at 0.1 μM reduced 20% of elastase activity; at 200 μM-the maximum concentration evaluated-inhibition was 68%. Both products had a dose-dependent effect. The Surfacen/inhibitor combination (0.5 mg/mL/80 µM) did not affect the surfactant interface property or the inhibitory activity of rCmPI-II against human neutrophil elastase.
CONCLUSIONS
Surfacen and the rCmPI-II inhibitor have an anti-elastase effect on an activated neutrophil model. rCmPI-II does not affect Surfacen's interface property and, therefore, both can be evaluated for combined use in treating inflammatory lung diseases.
Topics: Animals; Humans; Antiviral Agents; Leukocyte Elastase; Neutrophils; Protease Inhibitors; Pulmonary Surfactants; Swine
PubMed: 36417334
DOI: 10.37757/MR2022.V24.N3-4.7 -
American Journal of Respiratory Cell... Mar 2021
Topics: Animals; Diet; Dietary Carbohydrates; Feeding Behavior; Mice; Pulmonary Surfactants; Surface-Active Agents
PubMed: 33428544
DOI: 10.1165/rcmb.2020-0582ED -
Infection and Immunity Jul 2018The interactions between and the host environment at the site of infection are largely unknown. Pulmonary surfactant serves as an initial point of contact for inhaled...
The interactions between and the host environment at the site of infection are largely unknown. Pulmonary surfactant serves as an initial point of contact for inhaled bacteria entering the lung and is thought to contain molecular cues that aid colonization and pathogenesis. To gain insight into this ecological transition, we characterized the transcriptional response of MGH 78578 to purified pulmonary surfactant. This work revealed changes within the transcriptome that likely contribute to host colonization, adaptation, and virulence Notable transcripts expressed under these conditions include genes involved in capsule synthesis, lipopolysaccharide modification, antibiotic resistance, biofilm formation, and metabolism. In addition, we tested the contributions of other surfactant-induced transcripts to survival using engineered isogenic KPPR1 deletion strains in a murine model of acute pneumonia. In these infection studies, we identified the MdtJI polyamine efflux pump and the ProU glycine betaine ABC transporter to be significant mediators of survival within the lung and confirmed previous evidence for the importance of leucine synthesis to bacterial survival during infection. Finally, we determined that pulmonary surfactant promoted type 3 fimbria-mediated biofilm formation in and identified two surfactant constituents, phosphatidylcholine and cholesterol, that drive this response. This study provides novel insight into the interactions occurring between and the host at an important infection site and demonstrates the utility of purified lung surfactant preparations for dissecting host-lung pathogen interactions .
Topics: Amino Acids, Branched-Chain; Animals; Biofilms; Biogenic Polyamines; Fimbriae, Bacterial; Gene Expression Regulation, Bacterial; Host-Pathogen Interactions; Klebsiella pneumoniae; Male; Mice; Mice, Inbred C57BL; Pulmonary Surfactants; Virulence
PubMed: 29712730
DOI: 10.1128/IAI.00135-18 -
Neonatology 2019Exogenous surfactant replacement is the most effective evidence-based therapy for respiratory distress syndrome in preterm infants. The mode of administration has... (Review)
Review
Exogenous surfactant replacement is the most effective evidence-based therapy for respiratory distress syndrome in preterm infants. The mode of administration has evolved in the last decade towards less invasive techniques that aim to effectively provide an adequate dose of surfactant, while allowing spontaneous respiration to continue, and with the support of continuous positive airway pressure. Surfactant delivery via aerosolisation, pharyngeal instillation, and laryngeal mask are being actively pursued in research, but have not yet been adopted to any significant degree in clinical practice. Surfactant administration via thin catheter, on the other hand, is becoming more widely used in neonatal intensive care units worldwide and is now an acknowledged alternative to the standard mode of surfactant delivery. Different devices, including nasogastric tubes, vascular catheters, and purpose-built surfactant instillation catheters are used. We present here a contemporary review of surfactant administration via thin catheter, in a practical guide format that reflects the individual and collective scientific opinions of the clinicians who participated in formulating the guide.
Topics: Catheterization; Catheters; Equipment Design; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Lung; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; Treatment Outcome
PubMed: 31461712
DOI: 10.1159/000502610 -
The Journal of Biological Chemistry Mar 2019Toll-like receptors (TLRs) coupled to intracellular signaling cascades function as central elements of innate immunity that control transcription of numerous... (Review)
Review
Toll-like receptors (TLRs) coupled to intracellular signaling cascades function as central elements of innate immunity that control transcription of numerous pro-inflammatory genes. Two minor anionic phospholipids present in the pulmonary surfactant complex, palmitoyl-oleoyl-phosphatidylglycerol (POPG) and phosphatidylinositol (PI), antagonize the cognate ligand activation of TLRs 2 and 4. The lipids block recognition of activating ligands by the TLRs, either directly or via the TLR4 coreceptors CD14 and MD2. Antagonism of TLR activation results in inhibition of the initiating step of the pro-inflammatory signaling pathways. Evidence for this mechanism of action comes from direct binding studies between CD14 and MD2 with POPG and PI. Additional evidence for this mechanism of antagonism also comes from monitoring the reduction of protein phosphorylation events that characterize the intracellular signaling by activated TLRs. The pathogenesis of respiratory syncytial virus (RSV) and influenza A virus (IAV) have been linked to TLR4 activation, and we examined the action of POPG and PI as potential antagonists of the pathology of these viruses. Surprisingly, POPG and PI dramatically curtail infection, in addition to inhibiting inflammatory sequelae associated with RSV and IAV infections. The mechanism of action by the lipids is disruption of virus particle binding to host cell plasma membrane receptors, required for viral uptake. The antagonism of activation of TLRs and virus binding to the alveolar epithelium by resident constituents of the pulmonary surfactant system suggests that POPG and PI function in homeostasis, to prevent inflammatory processes that result in reductions in gas exchange within the alveolar compartment.
Topics: Animals; Humans; Immunity, Innate; Influenza A virus; Phospholipids; Pulmonary Surfactants; Respiratory Syncytial Viruses; Respiratory Tract Infections
PubMed: 30733339
DOI: 10.1074/jbc.AW118.003229 -
Medical Hypotheses Nov 2020Pulmonary surfactant is considered to be one of the soaps. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the other enveloped viruses become very weak...
Pulmonary surfactant is considered to be one of the soaps. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the other enveloped viruses become very weak against surfactant. The SARS virus binds to angiotensin-converting enzyme (ACE2) receptor and causes pneumonia. In the lung, the ACE2 receptor sits on the top of lung cells known as alveolar epithelial type II (AE2) cells. These cells play an important role in producing surfactant. Pulmonary surfactant is believed to regulate the alveolar surface tension in mammalian lungs. To our knowledge, AE2 cells are believed to act as immunoregulatory cells; however, pulmonary surfactant itself has not been believed to act as a defender against the enveloped viruses. This study hypothesises that pulmonary surfactant may be a strong defender of enveloped viruses. Therefore, old coronaviruses merely cause pneumonia. On the contrary, new SARS-CoV-2 can suppress the production of surfactant that binds to the ACE2 of AE2 cells. The coronavirus can survive in the lung tissue because of the exhaustion of pulmonary surfactant.
Topics: Ambroxol; Angiotensin-Converting Enzyme 2; Bromhexine; COVID-19; Clinical Trials as Topic; Crystallography, X-Ray; Humans; Models, Theoretical; Phagocytosis; Pneumonia, Viral; Pregnenediones; Pulmonary Alveoli; Pulmonary Surfactants; SARS-CoV-2; Surface Tension; Surface-Active Agents; COVID-19 Drug Treatment
PubMed: 32590326
DOI: 10.1016/j.mehy.2020.110020 -
Ugeskrift For Laeger Nov 2021This review gives a summary of the development of a method to measure lung surfactant on gastric aspirate at birth in premature infants with the purpose to threat... (Review)
Review
This review gives a summary of the development of a method to measure lung surfactant on gastric aspirate at birth in premature infants with the purpose to threat respiratory distress syndrome early with targeted surfactant. Machine learning was used to create the algorithm, and a point-of-care spectrometer was constructed for use in the delivery room. The sensitivity was 91% and specificity 79% in a clinical trial. The same method was used to measure surfactant in tracheal fluid in patients with COVID-19 since lung surfactant may be diminished in these patients.
Topics: COVID-19; Humans; Infant; Infant, Newborn; Pulmonary Surfactants; Respiratory Distress Syndrome, Newborn; SARS-CoV-2; Surface-Active Agents
PubMed: 34761742
DOI: No ID Found -
Colloids and Surfaces. B, Biointerfaces Feb 2023Inhalation of harmful vaping additives has led to a series of lung illnesses. Some of the selected additives such as vitamin E acetate, and related molecules like...
Inhalation of harmful vaping additives has led to a series of lung illnesses. Some of the selected additives such as vitamin E acetate, and related molecules like vitamin E and cannabidiol, may interfere with the function of the lung surfactant. Proper lipid organization in lung surfactant is key to maintaining low surface tensions, which provides alveolar stability and effective gas exchange throughout respiration. Physiological surfactants, such as bovine lipid extract surfactant used to treat neonatal respiratory distress syndrome, serve as a good model for examining the potential effects of vape additives on proper function. We have found that all additives impede the surfactants' ability to efficiently reach high surface pressures as these systems displayed numerous shoulders throughout compression with accompanying defects to lipid organization. Moreover, the formation of lipid bilayer stacks in the film are hindered by the additives, most notably with vitamin e acetate. Loss of these stacks leave the film prone to buckling and collapse under high compression that occurs at the end of expiration. The data suggest that the additives may interfere with both proper lipid organization and the surfactant protein function.
Topics: Animals; Cattle; Pulmonary Surfactants; Surface-Active Agents; Vaping; Lung; Lipid Bilayers; Acetates
PubMed: 36630771
DOI: 10.1016/j.colsurfb.2023.113132 -
Drug Delivery Dec 2019Intra-tracheal instillation of budesonide using surfactant as a vehicle significantly decreased the incidence of bronchopulmonary dysplasia or death in preterm infants....
Intra-tracheal instillation of budesonide using surfactant as a vehicle significantly decreased the incidence of bronchopulmonary dysplasia or death in preterm infants. The formularity of surfactant supplemented with budesonide and biophysical and chemical stability of the suspension has not been well reported. The aims are to investigate the biophysical and chemical stability of two surfactant preparations, Survanta and Curosurf, supplemented with budesonide. Biophysical property of the surface tension of Survanta and Survanta/budesonide suspension and of Curosurf and Curosurf/budesonide suspension was conducted by a pulsating bubble surfactometer and by a drop shape tensiometer. Chemical stability of Survanta/budesonide and of Curosurf/budesonide suspensions was tested by high-performance liquid chromatography analysis (HPLC). Pulmonary distribution of Survanta/F-budesonide suspension was examined by a Nano/PET digital scan in rats. The Marangoni effect of Survanta, Curosurf, and budesonide was tested by digital high speed photography. For Survanta supplemented with budesonide, with a concentration ratio of ≥50, the surface tension-lowering activity was minimally affected. Similarly, the surface tension-lowering activity of Curosurf was not significantly affected by addition of budesonide, if the concentration ratio was ≥160. With these concentration ratios of both suspensions, HPLC analysis revealed no new compounds identified. Curosurf as compared to Survanta exhibited a significantly higher Marangoni effect. We conclude that with current dosage recommended for Survanta and Curosurf, both surfactant/budesonide suspensions are biophysically and chemically stable. Both surfactants can act as an effective vehicle for budesonide delivery.
Topics: Animals; Biological Products; Budesonide; Injection, Intratympanic; Lung; Male; Phospholipids; Pulmonary Surfactants; Rats; Rats, Sprague-Dawley; Surface Tension
PubMed: 31204848
DOI: 10.1080/10717544.2019.1618418 -
Annals of Anatomy = Anatomischer... Jan 2017Pulmonary surfactant is a lipid-protein complex that lines and stabilizes the respiratory interface in the alveoli, allowing for gas exchange during the breathing cycle.... (Review)
Review
Pulmonary surfactant is a lipid-protein complex that lines and stabilizes the respiratory interface in the alveoli, allowing for gas exchange during the breathing cycle. At the same time, surfactant constitutes the first line of lung defense against pathogens. This review presents an updated view on the processes involved in biogenesis and intracellular processing of newly synthesized and recycled surfactant components, as well as on the extracellular surfactant transformations before and after the formation of the surface active film at the air-water interface. Special attention is paid to the crucial regulation of surfactant homeostasis, because its disruption is associated with several lung pathologies.
Topics: Alveolar Epithelial Cells; Animals; Humans; Lung; Lung Diseases; Phospholipids; Pulmonary Alveoli; Pulmonary Surfactants; Respiratory Mechanics; Surface Properties
PubMed: 27773772
DOI: 10.1016/j.aanat.2016.09.008