Dysfunction of pulmonary surfactant mediated by phospholipid oxidation is cholesterol-dependent

Al-Saiedy, Mustafa; Pratt, Ryan; Lai, Patrick; Kerek, Evan; Joyce, Heidi; Prenner, Elmar J.; Green, Francis; Ling, Chang‐Chun; Veldhuizen, Ruud A. W.; Ghandorah, Salim; Amrein, Matthias

doi:10.1016/j.bbagen.2018.01.008

Cited by 12 publications

(7 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A large proportion of phospholipids in surfactant is made of desaturated dipalmitoylphosphatidylcholine (30–45%) and the remaining is composed of unsaturated phospholipid, of which the unsaturated phosphatidylcholine is >30% [ 38 ]. Unsaturated phospholipids in the pulmonary surfactant are vulnerable to oxidation following exposure to environmental toxicants [ 39 ]. To test if PM exposure oxidizes unsaturated phospholipids in the pulmonary surfactant, we employed clinical surfactant, BLES that contains surfactant phospholipids and surfactant proteins (SP–B and SP-C) and used for the treatment of respiratory distress syndrome.…”

Section: Resultsmentioning

confidence: 99%

Lipid peroxidation index of particulate matter: Novel metric for quantifying intrinsic oxidative potential and predicting toxic responses

et al. 2021

View full text Add to dashboard Cite

Using particulate matter (PM) mass as exposure metric does not reveal the intrinsic PM chemical characteristics or toxic potential, which is crucial for monitoring the sources of emission causing adverse health effects and developing risk mitigating strategies. Oxidative stress and ensuing lipid peroxidation (LPO) in the lung are crucial underlying mechanisms of action by which PM drives cardiorespiratory disease. In the current study, we have postulated and demonstrated that the intrinsic potential of PM to elicit LPO, defined as “LPO index” as a novel approach for characterizing oxidative potential of PM (PM OP ) and predicting biological toxicity. First, we exposed unsaturated phosphatidylcholine (PC), an abundant phospholipid in the cell membrane, pulmonary surfactant, and lipoproteins to PM and analyzed the total burden of LPO byproducts generated as a measure of LPO index using a LPO reporter dye, BODIPY-C11. PM exposure resulted in a concentration-dependent increase in LPO. Second, we developed a novel method to expose the captured serum apoB100 lipoprotein particles to PM or its constituents and assessed the levels of specific oxidized-phospholipid on apoB100 particles by immunoassay using E06 monoclonal antibody (mab) that recognizes only PC containing oxidized-phospholipids (Ox-PCs). The immunoassay was highly sensitive to evaluate the PM LPO index and was modifiable by metal quenchers and exogenous antioxidant and radical quenchers. Third, to prove the pathophysiological relevance of Ox-PCs, we found that PM exposure generates Ox-PCs in mice lungs, pulmonary surfactant and lung cells. Fourth, we observed that treatment of macrophages with BAL fluid from PM exposed mice or PM-exposed pulmonary surfactant stimulated IL-6 production, which was abrogated by neutralization of Ox-PCs by mab E06 suggesting that Ox-PCs in lungs are proinflammatory. Overall, our study suggests that Ox-PCs as a probe of PM LPO index is a biologically relevant pathogenic biomarker and has a high value for evaluating PM OP .

show abstract

Section: Resultsmentioning

confidence: 99%

Lipid peroxidation index of particulate matter: Novel metric for quantifying intrinsic oxidative potential and predicting toxic responses

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Natural PS contains a substantial fraction of neutral lipids, mainly cholesterol (~8 wt%), which modulate surfactant activity [38]. However, excessive cholesterol levels are known to interfere with normal surfactant function, possibly contributing to respiratory insufficiency [39,40]. As the manufacturing of Curosurf ® involves depletion of neutral lipids, including cholesterol and cholesteryl esters, the data shown in Figure 2 and in earlier reports seem to indicate that the presence of cholesterol is not strictly required for the siRNA delivery-promoting effect of SP-B.…”

Section: Resultsmentioning

confidence: 99%

Nanocarrier Lipid Composition Modulates the Impact of Pulmonary Surfactant Protein B (SP-B) on Cellular Delivery of siRNA

et al. 2019

View full text Add to dashboard Cite

Two decades since the discovery of the RNA interference (RNAi) pathway, we are now witnessing the approval of the first RNAi-based treatments with small interfering RNA (siRNA) drugs. Nevertheless, the widespread use of siRNA is limited by various extra- and intracellular barriers, requiring its encapsulation in a suitable (nanosized) delivery system. On the intracellular level, the endosomal membrane is a major barrier following endocytosis of siRNA-loaded nanoparticles in target cells and innovative materials to promote cytosolic siRNA delivery are highly sought after. We previously identified the endogenous lung surfactant protein B (SP-B) as siRNA delivery enhancer when reconstituted in (proteo) lipid-coated nanogels. It is known that the surface-active function of SP-B in the lung is influenced by the lipid composition of the lung surfactant. Here, we investigated the role of the lipid component on the siRNA delivery-promoting activity of SP-B proteolipid-coated nanogels in more detail. Our results clearly indicate that SP-B prefers fluid membranes with cholesterol not exceeding physiological levels. In addition, SP-B retains its activity in the presence of different classes of anionic lipids. In contrast, comparable fractions of SP-B did not promote the siRNA delivery potential of DOTAP:DOPE cationic liposomes. Finally, we demonstrate that the beneficial effect of lung surfactant on siRNA delivery is not limited to lung-related cell types, providing broader therapeutic opportunities in other tissues as well.

show abstract

“…In the case of ARDS, where the surface tension at air-liquid interface is high and constant due to the consumption of surfactant, the lungs can be opened with pressure half of that is needed for lung opening (20 cm H2O) [86,77]. one way of reducing the function of the lung surfactant is by the effect of oxidising agents such as free radicals, that liberated from leukocytes or other pollutants leading to various lung diseases [87,88]. Disturbing surfactant homeostasis by smoking or pollution as examples, leads to surfactant insufficiency or accumulation.…”

Section: Surfactant Deficiencymentioning

confidence: 99%

The Role of Pulmonary Surfactant in COVID-19 Understanding

Ettarhouni

Mezoughi

2021

IRJPAC

View full text Add to dashboard Cite

Background: In Covid-19 the virus infects the respiratory tract in human. When lung tissue becomes diseased, the walls and lining of the alveoli and capillaries are damaged. At this point lung compliance and ventilation decrease. Pulmonary surfactant that is produced and dispersed into alveolar space, has a significant role in understanding how heavily covid-19 interferes and infects lung cells. The importance of pulmonary surfactant in alveoli is to lower surface tension at air/liquid interface in the lung. This is achieved by reducing the work of breathing and preventing alveolar collapse. The main constituent of pulmonary surfactant is dipalmitoylphosphatidylcholine (DPPC) (C40H80NO8P). It is a phospholipid containing two non polar palmitic acid C16 chains as hydrophobic tails linked to a polar head group of a phosphatidylcholine (also known as lecithin). Rationale of the Review and Objective Method: When DPPC molecules are in contact with a polar solvent, micelles which grow further into bilayers are formed considering their cylindrical structures. This trait makes the whole structure of pulmonary surfactant as amphipathic and surface active molecules. The head group of phosphatidylcholine in the pulmonary surfactant is attracted by polar liquid molecules causing a reduction of the liquid surface tension. Conclusion: This review complements the quoted information analysing them theoretically and integrates recent advances in pulmonary surfactant research with the global pandemic.

show abstract

Dysfunction of pulmonary surfactant mediated by phospholipid oxidation is cholesterol-dependent

Cited by 12 publications

References 51 publications

Lipid peroxidation index of particulate matter: Novel metric for quantifying intrinsic oxidative potential and predicting toxic responses

Lipid peroxidation index of particulate matter: Novel metric for quantifying intrinsic oxidative potential and predicting toxic responses

Nanocarrier Lipid Composition Modulates the Impact of Pulmonary Surfactant Protein B (SP-B) on Cellular Delivery of siRNA

The Role of Pulmonary Surfactant in COVID-19 Understanding

Contact Info

Product

Resources

About