Surfactant proteins: role in lung physiology and disease in early life

doi:10.1053/prrv.2000.0123

Paediatric Respiratory Reviews

Volume 2, Issue 2, June 2001, Pages 151-158

https://doi.org/10.1053/prrv.2000.0123 Get rights and content

Abstract

Pulmonary surfactant is an amalgam of proteins and phospholipids which serves to maintain a low surface tension within the alveolar regions of the lungs during changes in lung volume. Recently, two of the surfactant proteins – A and D – have been characterised within the collectin family and found to play important roles in the non-specific host defence of the lung. The field of surfactant biology has attracted the attention of physiologists, biochemists, molecular biologists and clinical scientists in an effort to describe the nature and role of pulmonary surfactant in health and disease. This paper will review the history and content of discoveries in the field of surfactant biology together with pulmonary diseases related to surfactant deficiency or dysfunction.

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A homotetrameric hemoglobin expressed in alveolar epithelial cells increases blood oxygenation in high-altitude plateau pika (Ochotona curzoniae)
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We verified that δ was expressed in ATI cells, ATII cells, and LBs of plateau pikas. In vivo, ATI cells comprise much of the surface area of the alveolar epithelium and function in gas exchange (Williams, 2003; Bishop, 2004), whereas ATII cells are the primary producers of PS, which is essential for normal lung function and innate immunity (Mallory, 2001; Poynter and LeVine, 2003; Wright, 2003). Using TEM, we clearly observed the ATII cells of plateau pikas and structurally intact LBs, whereas ATI cells were without LBs.
The plateau pika (Ochotona curzoniae) is native to the Qinghai-Tibet Plateau. In this study, the gene that encodes a heme-binding protein in the pulmonary surfactant (PS) of the pika is identified. The protein is a homotetrameric hemoglobin (δ₄) encoded by HBD (δ). HBD is expressed in alveolar epithelial type II (ATII) and type I (ATI) cells, upregulated by hypoxia. δ₄ is secreted into alveolar cavities through osmiophilic multilamellar bodies. HBD expression is downregulated by RNAi, which significantly increases hypoxia-inducible factor 1α expression in lung tissue and red blood cells and hemoglobin and blood lactate concentrations but significantly decreases arterial partial pressure of oxygen (PaO₂). Our results indicate that plateau pikas physiologically show hypoxemia when HBD expression is downregulated. Therefore, specific HBD expression in the lungs helps plateau pikas to obtain oxygen under hypoxia by maintaining higher PaO₂. These findings provide insights into the adaptive mechanisms of plateau pikas to withstand high-altitude environments.
Effect of pulmonary surfactant on the dispersion of carbon nanoparticles
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Evidence has shown that inhaled nanoparticles can penetrate deeply into the peripheral areas of the lungs, where they come into directly contact with the pulmonary surfactant (PS), which is distributed in the alveolar lining [8,9]. PS is a mixture comprising approximately 90% lipids [mainly dipalmitoylphosphatidylcholine (DPPC)] and 10% surfactant-associated proteins (SP-A, SP-B, SP-C and SP-D) [10–12]. It can form a liquid film at the air-water interface of the alveoli, and it can reduce surface tension to a near-zero value, thereby enabling the alveolar-capillary film to maintain a large surface area that facilitates respiration [13,14].
Carbon nanoparticles (CNs) are widely used and there has been a great concern about their potential adverse effects on human health. CNs can directly interact with the pulmonary surfactant (PS) lining of alveoli, but the dispersion state of CNs at PS film has not yet been explored. Accumulating evidences indicated that the degree of dispersion of nanoparticles has a strong influence on their biological activities. This study investigated the effect of PS and its major components on the dispersion state of three representative CNs (fullerene C60, nano carbon powder, graphene oxide). The results demonstrated that suspended concentrations of all three CNs were lower in the presence of PS and its lipid component dipalmitoylphosphatidylcholine (DPPC) than in the presence of bovine serum album (BSA). Compared with PS and DPPC, BSA notably reduced the hydrodynamic diameters of CNs. In addition, the absolute zeta potentials of CNs in the presence of BSA was higher than those in the presence of PS or DPPC, and this result corresponds to the increase of surface oxygen contents of CNs, indicating that relatively high surface oxygen content is beneficial for the dispersion of CNs in alveolus. π-A isotherms demonstrated that the surface tension and phase behavior of PS were obviously altered in the presence of CNs. This study revealed the role of PS and different active components in the dispersion of CNs, which is helpful for deeply understanding CNs alveolar transport and the associated potential hazards to lung health.
Time-dependent recruitment effects in ventilated healthy and lung-injured rats: " Recruitment-memory"
2012, Respiratory Physiology and Neurobiology
Citation Excerpt :
Proteinous oedema, resulting from lung injury, furthermore leads to the inhibition of surfactant activity and as a consequence to lung collapse due to high surface tension. Since turnover time of surfactant is approximately 12 h or 10% per hour (Mallory, 2001), the experimental time would have been too short to allow surfactant to be rebuilt. Hypophase contains precursor material of surfactant from the type II pneumocytes and moves towards regions of high surface tension (Scarpelli, 1998), so in the healthy lungs there is some redistribution of surfactant.
We investigated the sustained effects of recruitment manoeuvres in terms of “recruitment memory” in healthy and lung injured rats. 46 ventilated rats were allocated to either the control (sham) or the lavage group. Two consecutive low-flow manoeuvres were performed before sham/lavage and hourly during a 2-h-observation period. The slopes of the inspiratory limbs of the two resulting pressure–volume loops were translated into compliance–volume curves. The difference between the two compliance curves was smaller after lavage (root-mean-square deviation: 0.065 ml/cmH₂O control group, 0.038 ml/cmH₂O lavage group; p < 0.05) and stayed small during the whole experiment. In the control group, the deviation was small after sham manoeuvre but increased throughout the experiment. Compliance gain after recruitment was higher in the control group (0.1 ml/cmH₂O) compared to the lavage group (0.02 ml/cmH₂O, p < 0.05). We conclude that lung lavage led to alveolar collapse not susceptible to recruitment manoeuvres. On the contrary in healthy lungs recruitment manoeuvres led to persistent lung recruitment which we interpret as recruitment memory.
Respiratory Disorders of the Newborn
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Hemoglobin is expressed by alveolar epithelial cells
2006, Journal of Biological Chemistry
Hemoglobin gene expression in non-erythroid cells has been previously reported in activated macrophages from adult mice and lens cells, and recent studies indicate that alveolar epithelial cells can be derived from hematopoietic stem cells. Our laboratory has now produced strong evidence that hemoglobin is expressed by alveolar type II (ATII) cells and Clara cells, the primary producers of pulmonary surfactant. ATII cells are also closely involved in innate immunity within the lung and are stem cells that differentiate into alveolar type I cells. Reverse transcriptase-PCR was used to measure the expression of transcripts from the α- and β-globin gene clusters in several human and rodent pulmonary epithelial cells. Surprisingly, the two major globin mRNAs characteristic of adult erythroid precursor cells were clearly expressed in human A549 and H441 cell lines, mouse MLE-15 cells, and primary ATII cells isolated from normal rat and mouse lungs. DNA sequencing verified that these PCR products were indeed the result of specific amplification of globin gene cDNAs. These alveolar epithelial cells also expressed the corresponding hemoglobin protein subunits as determined by Western blotting, and tandem mass spectrometry sequencing was used to verify the presence of both α- and β-globin polypeptides in rat primary ATII cells. The function of hemoglobin expression by cells of the pulmonary epithelium will be determined by future studies, but this novel finding could potentially have important implications for the physiology and pathology of the lung.
Dysfunctional lactate metabolism in human alveolar type II cells from idiopathic pulmonary fibrosis lung explant tissue
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SERIES : RARE CHRONIC DISEASESurfactant proteins: role in lung physiology and disease in early life

Abstract

Am J Obstet Gynecol

Genomics

Biochem Biophys Res Commun

Biophys J

J Biol Chem

Lancet

J Pediatr

J Pediatr

J Pediatr

Blood

Clin Immunol

Chest

Chest

Neue auffassungen uber einem Grund-befriff der Atemechanik

Gesamte Exp Med

Properties, function and origin of alveolar lining layer

Nature

Surface tension of lung extracts

Proc Soc Exp Biol Med

Surface properties in relation to atelectasis and hyaline membrane disease

Am J Dis Child

Composition of surface-active material isolated from beef lung

Proc Natl Acad Sci USA

The biochemical development of surface activity in mammalian lung. I. The surface-active phospholipids: the separation and distribution of surface-active lecithin in the lung of the developing rabbit fetus

Pediatr Res

Isolation of apoproteins from canine surface active material

Am J Physiol

Deficiency of surfactant protein B in congenital alveolar proteinosis

N Eng J Med

The pulmonary surfactant system: biochemical and clinical aspects

Lung

Immunomodulatory functions of surfactant

Physiol Rev

Regulation of pulmonary surfactant secretion and clearance

Annu Rev Physiol

Regulation of lung surfactant protein secretion

Am J Physiol

The absence of phosphatidylglycerol in surfactant

Pediatr Res

A proposed nomenclature of pulmonary surfactant-associated proteins

Am Rev Respir Dis

Purification and biochemical characterization of CP-4 (SP-D): a collagenous surfactant-associated protein

Biochemistry

Surfactant protein A is localized at the corners of the pulmonary tubular myelin lattice

J Histochem Cytochem

Surfactant proteins A and D increase in response to intratracheal lipopolysaccharide

Am J Respir Cell Mol Biol

Biphasic glucocorticoid regulation of surfactant protein-A: characterization of the inhibitory process

Am J Physiol

Interferon-gamma and synthesis of surfactant components by cultured human fetal lung

Am J Respir Cell Mol Biol

SERIES : RARE CHRONIC DISEASE
Surfactant proteins: role in lung physiology and disease in early life