Effect of lowering serum cholesterol on the composition of surfactant in adult rat lung

Davidson, Kate G.; Acton, S; Barr, Heather A.; Nicholas, Terence E.

doi:10.1152/ajplung.1997.272.1.l106

Cited by 13 publications

(12 citation statements)

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“…Furthermore, it has recently been demonstrated that mice fed a high cholesterol diet exhibit an increased level of serum cholesterol and that the surfactant obtained from these mice had increased cholesterol values with impaired biophysical function (24). However, Davidson et al (7) demonstrated that lowering levels of serum cholesterol by inhibiting the release of hepatic lipoproteins did not affect surfactant cholesterol levels, due to the ability of type II cells to synthesize cholesterol. These findings provide evidence that, at least in the uninjured lung, surfactant cholesterol arises from the serum and/or de novo synthesis.…”

Section: Discussionmentioning

confidence: 99%

Role of cholesterol in the biophysical dysfunction of surfactant in ventilator-induced lung injury

Vockeroth¹,

Gunasekara

Amrein

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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Mechanical ventilation may lead to an impairment of the endogenous surfactant system, which is one of the mechanisms by which this intervention contributes to the progression of acute lung injury. The most extensively studied mechanism of surfactant dysfunction is serum protein inhibition. However, recent studies indicate that hydrophobic components of surfactant may also contribute. It was hypothesized that elevated levels of cholesterol significantly contribute to surfactant dysfunction in ventilation-induced lung injury. Sprague-Dawley rats (n = 30) were randomized to either high-tidal volume or low-tidal volume ventilation and monitored for 2 h. Subsequently, the lungs were lavaged, surfactant was isolated, and the biophysical properties of this isolated surfactant were analyzed on a captive bubble surfactometer with and without the removal of cholesterol using methyl-beta-cyclodextrin. The results showed lower oxygenation values in the high-tidal volume group during the last 30 min of ventilation compared with the low-tidal volume group. Surfactant obtained from the high-tidal volume animals had a significant impairment in function compared with material from the low-tidal volume group. Removal of cholesterol from the high-tidal volume group improved the ability of the surfactant to reduce the surface tension to low values. Subsequent reconstitution of high-cholesterol values led to an impairment in surface activity. It is concluded that increased levels of cholesterol associated with endogenous surfactant represent a major contributor to the inhibition of surfactant function in ventilation-induced lung injury.

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Section: Discussionmentioning

confidence: 99%

Role of cholesterol in the biophysical dysfunction of surfactant in ventilator-induced lung injury

Vockeroth¹,

Gunasekara

Amrein

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…The remarkable ability of the lung to maintain fairly normal cholesterol and phospholipid levels in the face of these conditions is impressive. It has been shown that depressing the hepatic secretion of all serum lipoproteins for 3 days with 4-aminopyrazolo(3,4d)pyrimidine results in a parallel reduction of phospholipids in both the surfactant and lamellar body fractions, whereas cholesterol content remains unaltered (15,58). However, despite the profound reduction in plasma phospholipid and cholesterol over the lifetime of the ABCA1Ϫ/Ϫ mouse, there was a moderate enrichment in phospholipid levels in lung tissue and a significant cholesterol enrichment accompanied by pathological alterations.…”

Section: Discussionmentioning

confidence: 99%

Pulmonary abnormalities due to ABCA1 deficiency in mice

Bates¹,

Tao²,

Collins³

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

112

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Ϫ/Ϫ ) have been shown to have low-serum high-density lipoprotein and abnormal lung morphology. We examined alterations in the structure and function of lungs from Ϫ/Ϫ mice (DBA1/J). Electron microscopy of the diseased mouse lung revealed areas of focal disease confirming previous results (47). Lipid analysis of the lung tissue of Ϫ/Ϫ mice showed a 1.2-and 1.4-fold elevation in total phospholipid (PL) and saturated phosphatidylcholine, respectively, and a marked 50% enrichment in total cholesterol content predominately due to a 17.5-fold increase in cholesteryl ester compared with wild type (WT). Lung surfactant in the Ϫ/Ϫ mice was characterized by alveolar proteinosis (161%), a slight increase in total PL (124%), and a marked increase in free cholesterol (155%) compared with WT. Alveolar macrophages were enriched in cholesterol (4.8-fold) due to elevations in free cholesterol (2.4-fold) and in cholesteryl ester (14.8-fold) compared with WT macrophages. More PL mass was cleared from the alveolar space of Ϫ/Ϫ mice lungs, measured using intratracheal installation of 3 H-PL liposomes. Compared with WT mice, the Abca1 Ϫ/Ϫ mice demonstrated respiratory distress with rapid, shallow breathing. Thus the lungs of mice lacking ABCA1 protein demonstrated abnormal morphology and physiology, with alveolar proteinosis and cholesterol enrichment of tissue, surfactant, and macrophages. The results indicate that the activity of ABCA1 is important for the maintenance of normal lung lipid composition, structure, and function. lung; surfactant; type II cells; alveolar macrophages; cholesterol MAINTENANCE OF APPROPRIATE surface tension in the lung is the primary function of pulmonary surfactant, the lipid-protein mixture that lines the alveoli (for review, Ref. 33). Surfactant proteins (SP) are divided into two groups, the hydrophilic SP-A and SP-D and the hydrophobic SP-C and SP-B (for review, Ref. 64). The lipid moiety of surfactant is predominantly phospholipid with 10% cholesterol by weight (34); cholesterol represents 58% of the neutral lipid fraction (26). The relative distribution of cholesterol differs between the various subfractions of alveolar surfactant (24). In rat surfactant, cholesterol represents 18% of the total lipid in the large aggregate heavy subfraction that pellets after centrifugation at 60,000 g but is a major component (60% of total lipid) of the small aggregate light subfraction isolated at 100,000 g (24). The large aggregate is the most surface-active fraction of surfactant and contains most of the SPs (22). Although the lung is capable of de novo synthesis of cholesterol, the bulk of pulmonary cholesterol is provided by serum lipoproteins. Radiolabeled cholesterol from very low-density (VLDL), lowdensity (LDL), and high-density (HDL) lipoproteins is taken up promptly by the perfused rat lung and, subsequently, recovered from the surfactant fraction (26, 51, 56). Type II cells, known to be responsible for the synthesis and secretion of surfactant, bind and incorporate gold-conjugated VLDL, LDL, and HDL as ...

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“…Alveolar CHOL is purported to be derived primarily from serum lipoproteins via lamellar bodies (27). However, we have recently reported that lamellar bodies in fact contain little CHOL (12) and that CHOL and DPPC are handled independently (28). The role and source of CHOL in surfactant is unresolved.…”

Section: Cholesterolmentioning

confidence: 99%

“…Phospholipid classes were separated by high performance liquid chromatography (HPLC) ( Porasil Silica; Waters Millipore, Bedford, MA) as described by Pison and associates (11) and quantified using a mass detector (Model 750/14; Applied Chromatography System, Cheshire, UK) coupled to a Delta Chromatography Data System program (Digital Solutions, Margate, Australia), Sphingosine (Sigma Chemicals, St. Louis, MO) was included as an internal standard. Neutral lipids were separated by HPLC using a Waters 18 C Novapak column (Waters Millipore) and free cholesterol (CHOL) was quantified by its absorption at 210 nm (12).…”

Section: Surfactant Analysismentioning

confidence: 99%

Quantity and Structure of Surfactant Proteins Vary Among Patients with Alveolar Proteinosis

Doyle

Davidson

Barr

et al. 1998

Am J Respir Crit Care Med

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Alveolar proteinosis (AP) is an idiopathic condition characterized by excess alveolar surfactant. Although the surfactant proteins (SP) are known to be aberrant, little is known of their variation between patients or their abundance relative to the lipids. We have examined surfactant composition in lavage fluid from 16 normal subjects and 13 patients with AP, one of whom was lavaged on 11 occasions over approximately 13 mo. In this patient we have examined composition on each occasion and in each sequential lavage aliquot. Composition was constant between right and left lung, but it differed markedly between patients. The cholesterol/disaturated phospholipid ratios (CHOL/DSP) were invariably elevated, on average by approximately 7-fold, whereas the SP-A/DSP and SP-B/DSP ratios were generally elevated, in some cases by as much as approximately 40- and approximately 100-fold, respectively. Although AP lavage generally contained more non-thiol-dependent SP-A aggregates and low Mr isoforms, the two-dimensional immunochemical staining patterns varied between patients and right and left lung. In the patient lavaged on multiple occasions, the SP-A/DSP and SP-B/DSP ratios progressively decreased as the patient's condition resolved. Because the SP-B/SP-A ratio was normal in all cases, we suggest that structural changes to the proteins occurred secondarily and that caution must be used in comparing functional data derived using SP-A obtained from patients with AP.

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Effect of lowering serum cholesterol on the composition of surfactant in adult rat lung

Cited by 13 publications

References 0 publications

Role of cholesterol in the biophysical dysfunction of surfactant in ventilator-induced lung injury

Role of cholesterol in the biophysical dysfunction of surfactant in ventilator-induced lung injury

Pulmonary abnormalities due to ABCA1 deficiency in mice

Quantity and Structure of Surfactant Proteins Vary Among Patients with Alveolar Proteinosis

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