Evolution, Development, and Function of the Pulmonary Surfactant System in Normal and Perturbed Environments

Orgeig, Sandra; Morrison, Janna L.; Daniels, Christopher B.

doi:10.1002/cphy.c150003

Cited by 31 publications

(27 citation statements)

References 558 publications

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“…Additionally, intact surfactant prevents alveolar fluid accumulation [54]. Thus, degradation of surfactant reduces its anti-edematous capacity and may enhance alveolar edema [55].…”

Section: Structural Damagementioning

confidence: 99%

Lung infection caused by Pseudomonas aeruginosa in a CD26/DPP4 deficient F344 rat model

et al. 2019

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Background Pseudomonas aeruginosa (PA) is the most important opportunistic pathogen in causing nosocomial infections and, furthermore, poses a permanent threat for severe chronic infections in patients with cystic fibrosis or COPD. The transmembrane protein CD26 with dipeptidyl peptidase-4 (DPP4) activity shows an increased expression in inflamed tissue. We tested whether CD26/DPP4 deficiency leads to reduced inflammation and decreased structural damage when infected with PA. Methods CD26/DPP4 + and CD26/DPP4 − rats were instilled intratracheally with NaCl (controls) or with PA. Six hours later, bacterial distribution was detected with the in vivo imaging system 200 (IVIS). Lungs were then processed for molecular biology, light and electron microscopy and analyzed qualitatively, quantitatively and stereologically. Bacterial numbers were determined in homogenized lungs. Results Compared to saline treated controls, in both infected groups (1) the acinar airspace was significantly increased, (2) the volume density of the alveolar epithelium was significantly decreased, (3) the septal thickness was significantly reduced, (4) more than 40% of the alveolar epithelial surface was damaged, and up to 36% of the epithelial surface was covered with edema. In infected CD26 − rats, the increase in lung weight was significantly less pronounced, the portion of edematous alveolar airspace was significantly lower and the part of edema interspersed with PA was decreased significantly. Conclusions CD26/DPP4 deficiency resulted in reduced pulmonary edema under sublethal PA infection, implicating a role for CD26 in infection progression. The partly pronounced structural damage may mask further possible influences of CD26 on the inflammatory response.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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“…Additionally, intact surfactant prevents alveolar fluid accumulation [54]. Thus, degradation of surfactant reduces its anti-edematous capacity and may enhance alveolar edema [55].…”

Section: Structural Damagementioning

confidence: 99%

Lung infection caused by Pseudomonas aeruginosa in a CD26/DPP4 deficient F344 rat model

et al. 2019

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“…Pulmonary surfactant is a complex mixture of lipids and proteins that functions to reduce surface tension at the air–liquid interface, prevent alveolar collapse and promote pulmonary immunity (Goerke & Clements, ; Pérez‐Gil & Weaver, ; Orgeig et al . ). A reduction in surfactant production is associated with the pathogenesis of RDS in newborns (Avery & Mead, ).…”

Section: Introductionmentioning

confidence: 97%

Differential effects of late gestation maternal overnutrition on the regulation of surfactant maturation in fetal and postnatal life

Lock

McGillick

Orgeig

et al. 2017

The Journal of Physiology

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With the increasing incidence of obesity worldwide, the proportion of women entering pregnancy overweight or obese has increased dramatically. The fetus of an overnourished mother experiences numerous metabolic changes that may modulate lung development and hence successful transition to air breathing at birth. We used a sheep model of maternal late gestation overnutrition (LGON; from 115 days' gestation, term 147 ± 3 days) to determine the effect of exposure to an increased plane of nutrition in late gestation on lung development in the fetus (at 141 days' gestation) and the lamb (30 days after birth). We found a decrease in the numerical density of surfactant protein positive cells, as well as a reduction in mRNA expression of surfactant proteins (SFTP-A, -B and -C), a rate limiting enzyme in surfactant phospholipid synthesis (phosphate cytidylyltransferase 1, choline, α; PCYT1A), and glucose transporters (SLC2A1 and SLC2A4) in the fetal lung. In lambs at 30 days after birth, there were no differences between Control and LGON groups in the surfactant components that were downregulated in the LGON fetuses. However, mRNA expression of SFTP-A, PCYT1A, peroxisome proliferator activated receptor-γ, fatty acid synthase and fatty acid transport protein were increased in LGON lambs compared to controls. These results indicate a reduced capacity for surfactant production in late gestation. While these deficits are normalised by 30 days after birth, the lungs of LGON lambs exhibited altered glucose transport and fatty acid metabolism, which is consistent with an enhanced capacity for surfactant synthesis and restoration of surfactant maturity in these animals.

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“…However, other studies have failed to prove that circulating cholesterol ends up forming part of surfactant complexes (Orgeig and Daniels, 2001;Milos et al, 2016), suggesting that other possible sources must be taken into account. It is remarkable that cholesterol levels in surfactant are tightly regulated to ensure a proper breathing function, and they are able to increase and decrease extremely fast in response to changes in temperature or breathing rate (Doyle et al, 1994;Orgeig et al, 2011). This seems to imply that a cholesterol reservoir might exist in order to provide cholesterol at fast rates when an increase is required.…”

Section: Sp-c and Cholesterol Relationships In The Lung Surfactant Comentioning

confidence: 99%

Alveolar Dynamics and Beyond – The Importance of Surfactant Protein C and Cholesterol in Lung Homeostasis and Fibrosis

Treumann

Baumjohann

2020

Front. Physiol.

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Sehlmeyer et al. SP-C/Cholesterol Relationships in Alveoli diffusion through lipid membranes is not well understood. However, it has been proposed that the interactions between cholesterol and the acyl carbon chains in phospholipids (stabilized by Van der Waals' forces) (Wennberg et al., 2012) create tightly packed arrangements that limits small molecule diffusion (Zocher et al., 2013). By decreasing trans-gauche rotation of the phospholipid acyl chains, membrane rigidity increases (Cassera et al., 2002; Molugu and Brown, 2019) leading to less free volume and free pockets which may accommodate oxygen, therefore reducing its flux (its partition and diffusion) through membranes (Zuniga-Hertz and Patel, 2019). Mammals developed sophisticated organs to optimize the uptake of oxygen during the life essential breathing cycle. From conducting airways to the second biggest surface exposed to the environment, the alveolar human surface (Ochs et al., 2004). In addition, the first membrane that oxygen encounters in the mammalian lungs is a complex mixture of lipids (mainly phosphatidylcholines (PC), such as dipalmitoylphosphatidylcholine (DPPC), up to a 90%) and proteins (10%) with a 5-10% of cholesterol (14-20% mol) (Zuo et al., 2008; Bernhard, 2016), called lung surfactant (surface active agent). Interestingly two surfaces in the human body present with abnormally higher cholesterol molar ratio, and both of them are in contact with the environment tightly regulating the uptake of oxygen. On the one hand, as previously explained, lung surfactant presents around a 14-20% mol cholesterol in its composition. On the other hand the eye lens surface contains up to 35% mol of cholesterol (Raguz et al., 2008; Mainali et al., 2013), compared to a normal cell plasma membrane with a 0.5 phospholipid to cholesterol molar ratio (van Meer et al., 2008; Widomska et al., 2017). Although the main function of lung Abbreviations: α-SMA, alpha smooth muscle actin; aaAMs, alternatively activated alveolar macrophages; ABCA1, ATP binding cassette transporter A1; ABCG1, ATP binding cassette transporter G1; ADA, adenosine-deaminase; ADP, adenosine diphosphate; AEC, alveolar epithelial cell; AE1C, alveolar epithelial type 1 cell; AE2C, alveolar epithelial type 2 cell; ALI

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Evolution, Development, and Function of the Pulmonary Surfactant System in Normal and Perturbed Environments

Cited by 31 publications

References 558 publications

Lung infection caused by Pseudomonas aeruginosa in a CD26/DPP4 deficient F344 rat model

Lung infection caused by Pseudomonas aeruginosa in a CD26/DPP4 deficient F344 rat model

Differential effects of late gestation maternal overnutrition on the regulation of surfactant maturation in fetal and postnatal life

Alveolar Dynamics and Beyond – The Importance of Surfactant Protein C and Cholesterol in Lung Homeostasis and Fibrosis

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