DOCSLIB.ORG

Understanding the Principle Biophysics Concepts of Pulmonary Surfactant in Health and Disease Chiara Autilio,1,2 Jesús Pérez-Gil1,2

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Understanding the Principle Biophysics Concepts of Pulmonary Surfactant in Health and Disease Chiara Autilio,1,2 Jesús Pérez-Gil1,2 Arch Dis Child Fetal Neonatal Ed: first published as 10.1136/archdischild-2018-315413 on 14 December 2018. Downloaded from Review Understanding the principle biophysics concepts of pulmonary surfactant in health and disease Chiara Autilio,1,2 Jesús Pérez-Gil1,2 1Department of Biochemistry ABSTRact stable film at the air-liquid interface, displacing and Molecular Biology, Faculty Pulmonary surfactant (PS) is a lipid-protein complex water molecules from exposure to air and therefore of Biology, Complutense reduces surface tension (figure 1A). At the same University, Madrid, Spain essential to stabilise the delicate structure of mammalian 2Research Institute "Hospital alveoli along with successive compression-expansion time, different components of PS constitute a first 12 de Octubre", Complutense respiratory cycles. To do so, surfactant reduces barrier to the access of pathogens to the rest of the University, Madrid, Spain dramatically surface tension at the air-liquid interface, organism via the large respiratory surface. an activity that depends critically on a proper lipid The major components of PS are lipids (~92%), Correspondence to composition and the presence of some specific surfactant mostly saturated phosphatidylcholine (DPPC) Professor Jesús Pérez-Gil, Department of Biochemistry, proteins. Lack or dysfunction of this system is associated (~40%), which is essential for PS surface active Faculty of Biology, Complutense with severe respiratory pathologies, which are in some properties. The saturated nature of acyl chains in University, José Antonio Novais cases treated by supplementation with exogenous DPPC allows for maximal packing on reduction of 12, Madrid 28040, Spain ; surfactant materials. The biophysical function and surface area, and therefore, maximal exclusion of jperezgil@ bio. ucm. es performance of PS, in health and disease, are directly water molecules and maximal reduction in surface Received 8 October 2018 influenced by its composition, structure and mechanical tension. Unsaturated phosphatidylcholine (PC), Revised 15 November 2018 properties. This review summarises the main biophysics phosphatidylglycerol (PG) and cholesterol account Accepted 16 November 2018 concepts behind the mechanisms that define surfactant for ~25%, ~10% and ~5–8% of PS total mass, function in a healthy lung and in pathological situations. respectively, whereas the other lipid species (neutral It also revises some of the most useful biophysical lipids and other phospholipids (PL)) correspond to techniques that provide information about surfactant- the residual 8–10% (figure 1B).1 The remaining related processes. Finally, translational biophysics will part of PS (~8%) is constituted by four specific be invoked to illustrate how biophysical studies may proteins, which can be classified into two families: by copyright. contribute to understand the role of surfactant in health SP-B and SP-C (hydrophobic) and SP-A and SP-D and disease and to design better surfactant-based (hydrophilic). SP-A, SP-B and SP-C are associated therapeutic approaches. to PS membranes, mainly binding negative-charged PLs (SP-B, SP-C) and DPPC (SP-A), and are essen- tial to facilitate formation of the PS interfacial film, organising and stabilising the structure, and PULMONARY SURFACTANT IN HEALTH AND ensuring correct recycling (figure 1B). Moreover, DISEASE SP-A and SP-D belong to the collectin protein family Pulmonary surfactant (PS) is a membrane-based and are involved in innate immune defence against system composed of a mixture of lipids and proteins. lung pathogens and allergens.2 3 It is synthetised by alveolar type II pneumocytes The composition, structure and mechanical prop- and secreted into the thin layer of fluid that covers erties of PS layers are directly responsible for the the alveolar epithelium. The main function of PS biophysical function and performance of the system is related to the stabilisation of the delicate struc- in a healthy lung. The lack, deficiency or inactiva- ture of mammalian alveoli by producing a dramatic tion of PS leads to severe respiratory disorders both http://fn.bmj.com/ reduction of the surface tension at the respiratory in neonates and adults, such as neonatal respira- air-liquid interface. At this interface, water mole- tory distress syndrome (RDS) and acute respiratory cules in contact with air cohere more strongly, distress syndrome (ARDS). because the interactions with the water bulk phase RDS is mostly due to lung immaturity and lack of are not compensated with interactions on the air side PS in preterm neonates. The resulting high surface where water molecules in vapour phase are scarce. tension impedes keeping the alveoli open since on 17 December 2018 by guest. Protected This generates a net intermolecular cohesive force, the first breath, causing high neonatal mortality which is defined as the surface tension. Opening (figure 1C left). In the early 1990s, surfactant new surface exposed to air, as required during each replacement therapy (SRT) with an exogenous © Author(s) (or their single inspiration, demands overcoming this cohe- surfactant preparation contributed to decreasing employer(s)) 2018. No sive superficial force, supplying the energy neces- mortality rates,4 as it facilitates respiratory commercial re-use. See rights sary to break the molecular interactions that the mechanics, which stimulates the self-production and permissions. Published 5 6 by BMJ. new molecules need to break through the gas-liquid of PS in newborns. However, SRT is not effec- interface. At high surface tension, therefore, the tive when RDS is due to severe genetic disorders To cite: Autilio C, Pérez-Gil J. work of breathing, that is, to open the lungs 15–20 (for instance, SP-B deficiency due to mutations in Arch Dis Child Fetal Neonatal Ed Epub ahead of print: times/min, would consume a fair proportion of the SFTPB gene or alterations in the ABCA3 gene) [please include Day Month metabolic energy, and would unavoidably end in and particularly challenged in pathologies in which Year]. doi:10.1136/ alveolar collapse. To prevent collapse and reduce both endogenous and therapeutic surfactant result archdischild-2018-315413 the work of breathing, PS spontaneously forms a inactivated by a direct or indirect damage of their Autilio C, Pérez-Gil J. Arch Dis Child Fetal Neonatal Ed 2018;0:F1–F9. doi:10.1136/archdischild-2018-315413 F1 Arch Dis Child Fetal Neonatal Ed: first published as 10.1136/archdischild-2018-315413 on 14 December 2018. Downloaded from Review Figure 1 Pulmonary surfactant (PS) in healthy and diseased human lung tissue. (A) Illustrative scheme of PL-mediated reduction of surface by copyright. tension. When a layer of PLs is formed at the air-liquid interface, the PL amphipathic molecules displace water molecules and reduce the air-liquid proximity. (B) A schematic representation of a normal alveolus, with the organisation of PS membranes at the air-liquid interface and the lipid/protein composition of lung surfactant. (C) Collapsed alveolus in RDS due to ATII cell immaturity and injured alveoli both in ARDS and MAS. The resulting inhibition of PS membranes caused by protein exudate, sPLA2, reactive oxygen species (ROS) production, cholesterol and bile acids is shown. (D) A schematic representation of (1) IPF alveolus with a reduction in levels of both SP-C and PLs and (2) PAP alveolus obstruction due to the excess of already used and undegraded PS. aAMφ, activated macrophages; AMφ, alveolar macrophages; aPMN, activated polymorphonucleated cells; ARDS, acute respiratory distress syndrome; ATI, alveolar type I pneumocytes; ATII, alveolar type II pneumocytes; BA, bile acid; CHOL, cholesterol; DPPC, saturated dipalmitoylphosphatidylcholine; FFA, free fatty acids; imATII, immature alveolar type II pneumocytes; IPF, idiopathic pulmonary fibrosis; MAS, meconium aspiration syndrome; MFB, myofibroblasts; MO, monocytes; n-ATI, necrotic alveolar type I pneumocytes; NL, neutral lipid; ox-PLs, oxidised phospholipids; ox-SP-B, oxidised SP-B; ox-SP-C, oxidised SP-C; PAP, pulmonary alveolar proteinosis; PG, phosphatidylglycerol; PL, phospholipid; RBC, red blood cell; RDS, respiratory distress syndrome; sPLA2, secretory phospholipase A2; unPC, unsaturated phosphatidylcholine. surface properties.7 Still, SRT seems to exhibit partial efficiency by means of the same compounds described above, which may be in some cases of ARDS. The identification of which patients with found in the meconium mixture.6 11 Besides, a simultaneous action http://fn.bmj.com/ ARDS can benefit the most is an important challenge in clinical of cholesterol and bile acids highly increases surfactant fluidity and research. contributes further to its inactivation (Figure 1C right).12 More- ARDS is an acute respiratory failure triggered by various over, bile acids act as a cofactor of sPLA2, increasing the enzyme conditions, characterised by extensive lung inflammation and activity and contributing to lung injury.13 diffuse alveolar injury. The resulting impairment of PS is mainly Although less relevant in a paediatric context, some reports due to an increase of infiltrating inflammatory cells, necrotic suggest that PS dysfunction could be also behind idiopathic on 17 December 2018 by guest. Protected cell fractions and exosomes. However, higher levels of secretory pulmonary fibrosis (IPF), a chronic and progressive epithelial phospholipase A2 (sPLA2) may also contribute to hydrolyse PLs injury which still nowadays remains unsolved. Specifically, a and nourish
Load more

Recommended publications
  • Effects of Surfactants on the Toxicitiy of Glyphosate, with Specific Reference to RODEO
    SERA TR 97-206-1b Effects of Surfactants on the Toxicitiy of Glyphosate, with Specific Reference to RODEO Submitted to: Leslie Rubin, COTR Animal and Plant Health Inspection Service (APHIS) Biotechnology, Biologics and Environmental Protection Environmental Analysis and Documentation United States Department of Agriculture Suite 5A44, Unit 149 4700 River Road Riverdale, MD 20737 Task No. 5 USDA Contract No. 53-3187-5-12 USDA Order No. 43-3187-7-0028 Prepared by: Gary L. Diamond Syracuse Research Corporation Merrill Lane Syracuse, NY 13210 and Patrick R. Durkin Syracuse Environmental Research Associates, Inc. 5100 Highbridge St., 42C Fayetteville, New York 13066-0950 Telephone: (315) 637-9560 Fax: (315) 637-0445 CompuServe: 71151,64 Internet: [email protected] February 6, 1997 TABLE OF CONTENTS EXECUTIVE SUMMARY ......................................... iii 1. INTRODUCTION .............................................1 2. CONSTITUENTS OF SURFACTANT FORMULATIONS USED WITH RODE0 ....4 2.1. AGRI-DEX ..........................................4 2.2. LI-700 .............................................4 2.3. R-11 ...............................................6 2.4. LATRON AG-98 ......................................6 2.5. LATRON AG-98 AG ....................................7 3. INFORMATION ON EFFECTS OF SURFACTANT FORMULATIONS ON THE TOXICITY OF RODEO ................................8 3.1. HUMAN HEALTH ......................................8 3.1.1. LI 700 ........................................8 3.1.2. Phosphatidylcholine ................................8
    [Show full text]
  • Pulmonary Surfactant: the Key to the Evolution of Air Breathing Christopher B
    Pulmonary Surfactant: The Key to the Evolution of Air Breathing Christopher B. Daniels and Sandra Orgeig Department of Environmental Biology, University of Adelaide, Adelaide, South Australia 5005, Australia Pulmonary surfactant controls the surface tension at the air-liquid interface within the lung. This sys- tem had a single evolutionary origin that predates the evolution of the vertebrates and lungs. The lipid composition of surfactant has been subjected to evolutionary selection pressures, partic- ularly temperature, throughout the evolution of the vertebrates. ungs have evolved independently on several occasions pendent units, do not necessarily stretch upon inflation but Lover the past 300 million years in association with the radi- unpleat or unfold in a complex manner. Moreover, the many ation and diversification of the vertebrates, such that all major fluid-filled corners and crevices in the alveoli open and close vertebrate groups have members with lungs. However, lungs as the lung inflates and deflates. differ considerably in structure, embryological origin, and Surfactant in nonmammals exhibits an antiadhesive func- function between vertebrate groups. The bronchoalveolar lung tion, lining the interface between apposed epithelial surfaces of mammals is a branching “tree” of tubes leading to millions within regions of a collapsed lung. As the two apposing sur- of tiny respiratory exchange units, termed alveoli. In humans faces peel apart, the lipids rise to the surface of the hypophase there are ~25 branches and 300 million alveoli. This structure fluid at the expanding gas-liquid interface and lower the sur- allows for the generation of an enormous respiratory surface face tension of this fluid, thereby decreasing the work required area (up to 70 m2 in adult humans).
    [Show full text]
  • Henry's Law Constants and Micellar Partitioning of Volatile Organic
    38 J. Chem. Eng. Data 2000, 45, 38-47 Henry’s Law Constants and Micellar Partitioning of Volatile Organic Compounds in Surfactant Solutions Leland M. Vane* and Eugene L. Giroux United States Environmental Protection Agency, National Risk Management Research Laboratory, 26 West Martin Luther King Drive, Cincinnati, Ohio 45268 Partitioning of volatile organic compounds (VOCs) into surfactant micelles affects the apparent vapor- liquid equilibrium of VOCs in surfactant solutions. This partitioning will complicate removal of VOCs from surfactant solutions by standard separation processes. Headspace experiments were performed to quantify the effect of four anionic surfactants and one nonionic surfactant on the Henry’s law constants of 1,1,1-trichloroethane, trichloroethylene, toluene, and tetrachloroethylene at temperatures ranging from 30 to 60 °C. Although the Henry’s law constant increased markedly with temperature for all solutions, the amount of VOC in micelles relative to that in the extramicellar region was comparatively insensitive to temperature. The effect of adding sodium chloride and isopropyl alcohol as cosolutes also was evaluated. Significant partitioning of VOCs into micelles was observed, with the micellar partitioning coefficient (tendency to partition from water into micelle) increasing according to the following series: trichloroethane < trichloroethylene < toluene < tetrachloroethylene. The addition of surfactant was capable of reversing the normal sequence observed in Henry’s law constants for these four VOCs. Introduction have long taken advantage of the high Hc values for these compounds. In the engineering field, the most common Vast quantities of organic solvents have been disposed method of dealing with chlorinated solvents dissolved in of in a manner which impacts human health and the groundwater is “pump & treat”swithdrawal of ground- environment.
    [Show full text]
  • Dive Theory Guide
    DIVE THEORY STUDY GUIDE by Rod Abbotson CD69259 © 2010 Dive Aqaba Guidelines for studying: Study each area in order as the theory from one subject is used to build upon the theory in the next subject. When you have completed a subject, take tests and exams in that subject to make sure you understand everything before moving on. If you try to jump around or don’t completely understand something; this can lead to gaps in your knowledge. You need to apply the knowledge in earlier sections to understand the concepts in later sections... If you study this way you will retain all of the information and you will have no problems with any PADI dive theory exams you may take in the future. Before completing the section on decompression theory and the RDP make sure you are thoroughly familiar with the RDP, both Wheel and table versions. Use the appropriate instructions for use guides which come with the product. Contents Section One PHYSICS ………………………………………………page 2 Section Two PHYSIOLOGY………………………………………….page 11 Section Three DECOMPRESSION THEORY & THE RDP….……..page 21 Section Four EQUIPMENT……………………………………………page 27 Section Five SKILLS & ENVIRONMENT…………………………...page 36 PHYSICS SECTION ONE Light: The speed of light changes as it passes through different things such as air, glass and water. This affects the way we see things underwater with a diving mask. As the light passes through the glass of the mask and the air space, the difference in speed causes the light rays to bend; this is called refraction. To the diver wearing a normal diving mask objects appear to be larger and closer than they actually are.
    [Show full text]
  • Biomechanics of Safe Ascents Workshop
    PROCEEDINGS OF BIOMECHANICS OF SAFE ASCENTS WORKSHOP — 10 ft E 30 ft TIME AMERICAN ACADEMY OF UNDERWATER SCIENCES September 25 - 27, 1989 Woods Hole, Massachusetts Proceedings of the AAUS Biomechanics of Safe Ascents Workshop Michael A. Lang and Glen H. Egstrom, (Editors) Copyright © 1990 by AMERICAN ACADEMY OF UNDERWATER SCIENCES 947 Newhall Street Costa Mesa, CA 92627 All Rights Reserved No part of this book may be reproduced in any form by photostat, microfilm, or any other means, without written permission from the publishers Copies of these Proceedings can be purchased from AAUS at the above address This workshop was sponsored in part by the National Oceanic and Atmospheric Administration (NOAA), Department of Commerce, under grant number 40AANR902932, through the Office of Undersea Research, and in part by the Diving Equipment Manufacturers Association (DEMA), and in part by the American Academy of Underwater Sciences (AAUS). The U.S. Government is authorized to produce and distribute reprints for governmental purposes notwithstanding the copyright notation that appears above. Opinions presented at the Workshop and in the Proceedings are those of the contributors, and do not necessarily reflect those of the American Academy of Underwater Sciences PROCEEDINGS OF THE AMERICAN ACADEMY OF UNDERWATER SCIENCES BIOMECHANICS OF SAFE ASCENTS WORKSHOP WHOI/MBL Woods Hole, Massachusetts September 25 - 27, 1989 MICHAEL A. LANG GLEN H. EGSTROM Editors American Academy of Underwater Sciences 947 Newhall Street, Costa Mesa, California 92627 U.S.A. An American Academy of Underwater Sciences Diving Safety Publication AAUSDSP-BSA-01-90 CONTENTS Preface i About AAUS ii Executive Summary iii Acknowledgments v Session 1: Introductory Session Welcoming address - Michael A.
    [Show full text]
  • Effect of Surfactant on Interfacial Gas Transfer Studied by Axisymmetric Drop Shape Analysis-Captive Bubble (ADSA-CB)
    5446 Langmuir 2005, 21, 5446-5452 Effect of Surfactant on Interfacial Gas Transfer Studied by Axisymmetric Drop Shape Analysis-Captive Bubble (ADSA-CB) Yi Y. Zuo,† Dongqing Li,† Edgar Acosta,‡ Peter N. Cox,§ and A. Wilhelm Neumann*,† Department of Mechanical and Industrial Engineering, University of Toronto, 5 King’s College Road, Toronto, ON, M5S 3G8, Canada, Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, ON, M5S 3E5, Canada, and Department of Critical Care Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada Received January 31, 2005. In Final Form: April 3, 2005 A new method combining axisymmetric drop shape analysis (ADSA) and a captive bubble (CB) is proposed to study the effect of surfactant on interfacial gas transfer. In this method, gas transfer from a static CB to the surrounding quiescent liquid is continuously recorded for a short period (i.e., 5 min). By photographical analysis, ADSA-CB is capable of yielding detailed information pertinent to the surface tension and geometry of the CB, e.g., bubble area, volume, curvature at the apex, and the contact radius and height of the bubble. A steady-state mass transfer model is established to evaluate the mass transfer coefficient on the basis of the output of ADSA-CB. In this way, we are able to develop a working prototype capable of simultaneously measuring dynamic surface tension and interfacial gas transfer. Other advantages of this method are that it allows for the study of very low surface tensions (<5 mJ/m2) and does not require equilibrium of gas transfer.
    [Show full text]
  • Perspectives on Mucus Secretion in Reef Corals
    MARINE ECOLOGY PROGRESS SERIES Vol. 296: 291–309, 2005 Published July 12 Mar Ecol Prog Ser REVIEW Perspectives on mucus secretion in reef corals B. E. Brown*, J. C. Bythell School of Biology, Newcastle University, Newcastle upon Tyne NE1 7RU, UK ABSTRACT: The coral surface mucus layer provides a vital interface between the coral epithelium and the seawater environment and mucus acts in defence against a wide range of environmental stresses, in ciliary-mucus feeding and in sediment cleansing, amongst other roles. However, we know surpris- ingly little about the in situ physical and chemical properties of the layer, or its dynamics of formation. We review the nature of coral mucus and its derivation and outline the wide array of roles that are pro- posed for mucus secretion in corals. Finally, we review models of the surface mucus layer formation. We argue that at any one time, different types of mucus secretions may be produced at different sites within the coral colony and that mucus layers secreted by the coral may not be single homogeneous layers but consist of separate layers with different properties. This requires a much more dynamic view of mucus than has been considered before and has important implications, not least for bacterial colonisation. Understanding the formation and dynamics of the surface mucus layer under different environmental conditions is critical to understanding a wide range of associated ecological processes. KEY WORDS: Mucin · Mucopolysaccharide · Coral surface microlayer · CSM · Surface mucopolysaccharide layer · SML Resale or republication not permitted without written consent of the publisher INTRODUCTION production has been a problem for many working with coral tissues in recent years, and the offending sub- The study of mucus secretion by corals has fascinated stance has to be removed before histological, biochem- scientists for almost a century, from the work of Duer- ical or physiological processing can begin.
    [Show full text]
  • Dive Kit List Intro
    Dive Kit List Intro We realise that for new divers the array of dive equipment available can be slightly daunting! The following guide should help you choose dive gear that is suitable for your Blue Ventures expedition, without going overboard. Each section will highlight features to consider when choosing equipment, taking into account both budget and quality. Diving equipment can be expensive so we don’t want you to invest in something that will turn out to be a waste of money or a liability during your expedition! Contents Must haves Mask Snorkel Fins Booties Exposure protection DSMB and reel Slate and pencils Dive computer Dive manuals Highly recommended Cutting tool Compass Underwater light Optional Regulator BCD Dry bag Extra stuff Contact us Mask Brands: Aqualung, Atomic, Cressi, Hollis, Mares, Oceanic, Scubapro, Tusa Recommended: Cressi Big Eyes. Great quality for a comparatively lower price. http://www.cressi.com/Catalogue/Details.asp?id=17 Oceanic Shadow Mask. Frameless mask, which makes it easy to put flat into your luggage or BCD pocket. http://www.oceanicuk.com/shadow-mask.html Aqualung Linea Mask. Keeps long hair from getting tangled in the buckle while also being frameless. https://www.aqualung.com/us/gear/masks/item/74-linea Tusa neoprene strap cover. Great accessory for your mask in order to keep your hair from getting tangled in the mask and increasing the ease of donning and doffing your mask. http://www.tusa.com/eu-en/Tusa/Accessories/MS-20_MASK_STRAP To be considered: The most important feature when you buy a mask is fit. The best way to find out if it is the right mask for you is to place the mask against your face as if you were wearing it without the strap, and inhaling through your nose.
    [Show full text]
  • What Happens to Herbicides After We Apply Them? by Kyra Clark
    Refuge Notebook • Vol. 19, No. 38 • September 22, 2017 What happens to herbicides after we apply them? by Kyra Clark some of the more than 110 exotic plant species in- troduced to the Kenai Peninsula. Over the years, we have been spot treating invasive plants at trail- heads and boat launches, keeping the refuge notice- ably cleaner than the rest of the peninsula. We typ- ically use three chemicals: glyphosate, aminopyralid and fluridone. These are the active ingredients in the different commercial herbicides we use to control or kill target species. The big differences between DDT and other pesti- cides used in Carson’s time and those we use now are their environmental fate and how they degrade over time. DDT has a half-life (time required for half of the original concentration to degrade) of 2–15 years. DDT can also leach into water sources and bio-accumulate in the tissues of animals. In contrast, the three chem- icals we use all have half-lives under a year, do not leach, and do not bio-accumulate in animals. There has been a lot of bad press about glyphosate, but most issues with glyphosate products are asso- ciated with its use in agriculture where herbicides are applied chronically or genetically encoded into seeds. Glyphosate products vary in their formula- tions of glyphosate, the carrier solution, and surfac- tant. Surfactants enhance the active ingredient’s ef- fectiveness by breaking surface tension of the liquid herbicide to improve its coverage of foliage, its ability to stick to foliage, and its rainfastness. We typically use two glyphosate formulations for terrestrial weed control on the refuge.
    [Show full text]
  • Pulmonary Surfactants and Their Role in Pathophysiology of Lung Disorders
    Indian Journal of Experimental Biology Vol. 51, January 2013, pp. 5-22 Review Article Pulmonary surfactants and their role in pathophysiology of lung disorders Aparna Akella & Shripad B Deshpande* Department of Physiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005, India Surfactant is an agent that decreases the surface tension between two media. The surface tension between gaseous- aqueous interphase in the lungs is decreased by the presence of a thin layer of fluid known as pulmonary surfactant. The pulmonary surfactant is produced by the alveolar type-II (AT-II) cells of the lungs. It is essential for efficient exchange of gases and for maintaining the structural integrity of alveoli. Surfactant is a secretory product, composed of lipids and proteins. Phosphatidylcholine and phosphatidylglycerol are the major lipid constituents and SP-A, SP-B, SP-C, SP-D are four types of surfactant associated proteins. The lipid and protein components are synthesized separately and are packaged into the lamellar bodies in the AT-II cells. Lamellar bodies are the main organelle for the synthesis and metabolism of surfactants. The synthesis, secretion and recycling of the surfactant lipids and proteins is regulated by complex genetic and metabolic mechanisms. The lipid-protein interaction is very important for the structural organization of surfactant monolayer and its functioning. Alterations in surfactant homeostasis or biophysical properties can result in surfactant insufficiency which may be responsible for diseases like respiratory distress syndrome, lung proteinosis, interstitial lung diseases and chronic lung diseases. The biochemical, physiological, developmental and clinical aspects of pulmonary surfactant are presented in this article to understand the pathophysiological mechanisms of these diseases.
    [Show full text]
  • Lipid–Protein and Protein–Protein Interactions in the Pulmonary Surfactant System and Their Role in Lung Homeostasis
    International Journal of Molecular Sciences Review Lipid–Protein and Protein–Protein Interactions in the Pulmonary Surfactant System and Their Role in Lung Homeostasis Olga Cañadas 1,2,Bárbara Olmeda 1,2, Alejandro Alonso 1,2 and Jesús Pérez-Gil 1,2,* 1 Departament of Biochemistry and Molecular Biology, Faculty of Biology, Complutense University, 28040 Madrid, Spain; [email protected] (O.C.); [email protected] (B.O.); [email protected] (A.A.) 2 Research Institut “Hospital Doce de Octubre (imasdoce)”, 28040 Madrid, Spain * Correspondence: [email protected]; Tel.: +34-913944994 Received: 9 May 2020; Accepted: 22 May 2020; Published: 25 May 2020 Abstract: Pulmonary surfactant is a lipid/protein complex synthesized by the alveolar epithelium and secreted into the airspaces, where it coats and protects the large respiratory air–liquid interface. Surfactant, assembled as a complex network of membranous structures, integrates elements in charge of reducing surface tension to a minimum along the breathing cycle, thus maintaining a large surface open to gas exchange and also protecting the lung and the body from the entrance of a myriad of potentially pathogenic entities. Different molecules in the surfactant establish a multivalent crosstalk with the epithelium, the immune system and the lung microbiota, constituting a crucial platform to sustain homeostasis, under health and disease. This review summarizes some of the most important molecules and interactions within lung surfactant and how multiple lipid–protein and protein–protein interactions contribute to the proper maintenance of an operative respiratory surface. Keywords: pulmonary surfactant film; surfactant metabolism; surface tension; respiratory air–liquid interface; inflammation; antimicrobial activity; apoptosis; efferocytosis; tissue repair 1.
    [Show full text]
  • Synthetic Surfactant with a Recombinant Surfactant Protein C Analogue Improves Lung Function and Attenuates Inflammation in a Mo
    Zebialowicz Ahlström et al. Respiratory Research (2019) 20:245 https://doi.org/10.1186/s12931-019-1220-x RESEARCH Open Access Synthetic surfactant with a recombinant surfactant protein C analogue improves lung function and attenuates inflammation in a model of acute respiratory distress syndrome in adult rabbits J. Zebialowicz Ahlström1†, F. Massaro2†, P. Mikolka1,3†, R. Feinstein4, G. Perchiazzi5, O. Basabe-Burgos1, T. Curstedt6, A. Larsson5, J. Johansson1 and A. Rising1,7* Abstract Aim: In acute respiratory distress syndrome (ARDS) damaged alveolar epithelium, leakage of plasma proteins into the alveolar space and inactivation of pulmonary surfactant lead to respiratory dysfunction. Lung function could potentially be restored with exogenous surfactant therapy, but clinical trials have so far been disappointing. These negative results may be explained by inactivation and/or too low doses of the administered surfactant. Surfactant based on a recombinant surfactant protein C analogue (rSP-C33Leu) is easy to produce and in this study we compared its effects on lung function and inflammation with a commercial surfactant preparation in an adult rabbit model of ARDS. Methods: ARDS was induced in adult New Zealand rabbits by mild lung-lavages followed by injurious ventilation (VT 20 m/kg body weight) until P/F ratio < 26.7 kPa. The animals were treated with two intratracheal boluses of 2.5 mL/kg of 2% rSP-C33Leu in DPPC/egg PC/POPG, 50:40:10 or poractant alfa (Curosurf®), both surfactants containing 80 mg phospholipids/mL, or air as control. The animals were subsequently ventilated (VT 8–9 m/kg body weight) for an additional 3 h and lung function parameters were recorded.
    [Show full text]