The Effect of Cholesterol on the Biophysical Inhibition of Pulmonary Surfactant by Albumin
Bibliographic record
Abstract
Pulmonary surfactant is a mixture of 85% phospholipids, 5–8% cholesterol and 5–8% surfactant proteins which forms a surface tension reducing lipid film at the air‐liquid interface of the alveoli. By reducing the surface tension to near 0mN/m values during compression (i.e. exhalation) surfactant maintains alveolar stability at low lung volumes and maintains proper lung compliance. The importance of surfactant is evident in Acute Respiratory Distress Syndrome (ARDS) in which the dysfunction of surfactant contributes to hypoxemia, regional areas of collapse and reduced lung compliance. Specifically, serum proteins, such as Albumin, leaking into the lung during ARDS have been shown to interfere with surfactant's ability to reach low surface tension. In addition, recent studies suggest that elevated cholesterol within surfactant also contribute to surfactant dysfunction in the setting of lung injury. Although the effects of cholesterol and serum proteins with surfactant have been studied independently, the interaction between the two has not previously been investigated. It was hypothesized that elevated levels of cholesterol within surfactant will make surfactant more susceptible to serum protein inhibition. Methods Bovine Lipid Extract Surfactant (BLES), a commercially available exogenous surfactant, was utilized and modified to generate samples with concentrations of 0, 2.5, 5 and 10% (w/w) cholesterol. Varying amounts of Bovine Serum Albumin (BSA) were subsequently added to each sample to attain concentrations of 0, 20, 30, 40 and 50 mg/ml. A constrained sessile drop surfactometer was used to determine the minimal achievable surface tensions during dynamic compression/expansion cycles. Results Samples with various levels of cholesterol, in the absence of BSA, reached minimum surface tension values of near 0mN/m during compression. At moderate levels of BSA (20 & 30mg/ml), minimum surface tensions were lower in surfactant samples containing cholesterol as compared to samples containing no cholesterol. Finally, at high BSA values, all surfactant samples had surface tension values that were higher than those at the lower BSA concentration but were not significantly different among the sample with different cholesterol concentrations. Discussion Contrary to the hypothesis, values of up to 10% cholesterol within surfactant do not appear to increase the susceptibility of surfactant to serum protein inhibition. In fact, the results suggest that cholesterol mitigates the effect of moderate levels of BSA on surfactant function. It is concluded that cholesterol within surfactant contributes to its resistance against inhibition by albumin. Support or Funding Information Canadian Institutes for Health Research.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".