DOCSLIB.ORG

Lung Phospholipids in the Embryonic and Immature Chicken: Changes in Lipid Composition and Biosynthesis During Maturation of the Surfactant System

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Lung Phospholipids in the Embryonic and Immature Chicken: Changes in Lipid Composition and Biosynthesis During Maturation of the Surfactant System THE JOURNAL OF EXPERIMENTAL ZOOLOGY 22031-80 (1982) Lung Phospholipids in the Embryonic and Immature Chicken: Changes in Lipid Composition and Biosynthesis During Maturation of the Surfactant System VINCENT W. HYLKA AND BYRON A. DONEEN Division of Biological Sciences, Department ofZoology, University ofMichigan, Ann Arbor. Michigan 48109 ABSTRACT Total phospholipid and its components were measured in lungs of the embryonic chick, and in tissue, lamellar bodies, and lavage fluid after hatching. Phosphatidylcholine (PC), the major phospholipid in surfactant, was fractionated and the amount and fatty acid composition of its disaturated (DSPC) component was determined. The synthetic rates of PC. DSPC, and other choline phospholipids were determined on days 14 and 19 of incubation from incorporation of "C-choline. Choline pool size was also estimated at these times. Phospholipid content of the lung increased most rapidly after day 18of incubation with the greatest increase in PC. The PC synthesized just prior to breathing was enriched in DSPC, which constituted 45% of PC on day 19 and only 30% on day 14. DSPC content was even lower in embryonic liver and yolk. Incorporation of I4C-cholinein vitro into pulmonary PC, Sphingomyelin (Sphingo),and DSPC was greater in birds before breathing (day 19) than in the younger embryos. Choline pool size decreased between days 14 and 19 of incubation, but the synthetic rate of DSPC doubled in this interval. Increased accumulation and biosynthesis of pulmonary PC, Sphingo, and DSPC in lung tissue of the embryo paralleled ap- pearance of lamellar bodies. In 5-6-week-old chickens the major pulmonary phospholipid was also DSPC. In lavage, 70% of PC was DSPC, predominantly dipalmitoyl PC. As in the mammalian lung, PC,especially its DSPC component, forms the major phospholipid of avian surfactant, and the synthesis of DSPC is specifically stimulated prior to breathing. The gasexchanging surface of the mammal- as measured by its capacity to synthesize and ian lung is lined with surfactant. By lowering secrete surfactant phospholipid, depends upon surface tension, surfactant prevents alveolar certain hormones (reviewed by Smith and collapse, reduces work expended in lung Bogues, '80; Hitchcock, '80; Ballard '81). expansion, and inhibits transddation of fluid As air capillaries in the avian lung are into air spaces (Levine and Mellins, '75; Van strengthened by connective tissue (Duncker, Golde, '76). Mammalian lung surfactant "71), this structure is more rigid than the mam- consists largely of phospholipid (85% by malian lung. The bird lung, therefore, might weight), and this is predominantly (70-80%) appear to have little requirement for a surface- phosphatidylcholine (PC) (honey, '79). The active lining. Ultrastructural examination, major surface-active component of surfactant however, revealed an osmiophilic lining in air is dipalmitoyl PC (containing two 16:O fatty spaces of the chicken, goose, and turkey (Tyler acids), which forms 60-70% of PC in lung lav- and Pangborn, '64; Lambson and Cohn, '68; age (Van Golde, '76). Lung surfactant is syn- Petrik and Riedel, '68a, b; Fujiwara et al., '70). thesized and stored in lamellar bodies, organ- This lining seems to be quite similar in bio- elles characteristic of type I1 pneumocytes chemistry and in function to mammalian sur- (Williams, '77). Maturation of the type I1 cell factant. Composition of major pulmonary 0022-104X/82/2201-0071$03.000 1982 ALAN R. LISS. INC. 72 V.W. HYLKA AND B.A. DONEEN phospholipids in the adult bird is nearly identi- before onset of ventilation, taking account of cal with mammalian lung (Harlan et al., '66; differences in choline pool size. Fujiwara et al., '70). Lung lavages from adult MATERIALS AND METHODS birds contain secreted surfactant, and these washings display a lipid composition and sur- Animals face tension properties similar to those of Fertilized eggs (Rhode Island Red X White mammals (Fujiwara et al., '70). Lamellar bod- Leghorn) were obtained from a local distribu- ies have also been identified in type I1 pneumo- tor (Dave's Eggs and Poultry, Ann Arbor, cytes of the avian pulmonary epithelium Michigan), and incubated at 37.7 f 0.7" in a (Dameron and Marin, '70; Marin et al. '78), and forced-draft, rocking incubator. Hatched buds these organelles are enriched in PC (Marin et were kept on a 12D:12L cycle and fed commer- al., '79). Pattle ('65, '78) and Duncker ('71, '78) cial poultry feed and water ad libitum. Onset of have proposed that structural rigidity of avian breathing in embryos was determined by ob- lung and pulmonary surfactant both promote serving whether pipping had occurred or if the distention of narrow air capillaries. Thus, ap beak was in the air space. In this study, all em pearance of surfactant in the embryonic bird bryos at 20 days of incubation had begun lung lung prior to the onset of ventilation may be as ventilation, whereas those at 19 days or crucial for hatching as it is for the birth of younger had not commenced breathing. mammals. The work of Tordet and Marin ('76) on the Lipid isolation and analysis embryonic chicken lung has emphasized the on- Tissues were rapidly dissected, blotted, togeny of two major classes of lung phospho- weighed, and quick-frozen in a dry-ice-ethanol lipids, PC and phosphatidylethanolamine(PE). bath. Yolk was obtained by pipetting a 300 pl These investigators (Marin et al., '79) also aliquot from the yolk sac, being careful to showed that PC content was enriched in avian avoid blood contamination. Tissues and yolk lung lavage and isolated lamellar bodies. In were stored at -25°C until analyzed. both studies, the major surface-active Total lipids were extracted by homogeniza- component of PC (i.e., DSPC) and other minor, tion with 20 volumes of ch1oroform:methanol though important, surfactant lipids (i.e., (21) according to the method of Folch et al. phosphatidylglycerol:PG, phosphatidylinosi- ('57). Total extracted fat was measured gravi- tol:PI, and Sphingomyelin: Sphingo) were not metrically following evaporation of solvent measured. Earlier work has also shown that in- and overnight desiccation in vacuo over KOH. corporation of I4C-cholineinto PC increases in In experiments involving choline incorpora- the bird lung prior to hatching (Compton and tion, an aliquot of the ch1oroform:methanol Goeringer, '81), but the significance of this homogenate was used for measurement of pro- conclusion must be questioned because the tein using bovine serum albumin as standard size and specific activity of the pulmonary cho- (Lowry et al., '51). line pool were not determined during onto- Individual phospholipid classes were ob- geny. Finally, no data are available to deter- tained by thin-layer chromatography (TLC) mine if lipid composition and certain pathways using Whatman LK5D precoated silica gel of phospholipid synthesis are unique to the plates. Lipid samples (500-900 pg) were applied developing lung as seems to be the case in the to TLC plates in a nitrogen atmosphere with mammal (Van Golde, '76). This information is standards run in parallel. Phospholipids were essential in view of the totally different pat- separated using ch1oroform:methanol:water tern of fat metabolism in the avian embryo (65:35:5, solvent system I)or ch1oroform:meth- which relies ultimately on stored yolk for lipid anol: 0.25CToKCl: 2-propano1:triethylamine(30: precursors (Doneen, '81). This paper fills major 9:6:25:18, solvent system 11) (Touchstone et gaps in our understanding of lung lipid metab- al., '80). Solvent system I1 was utilized for olism in the developing bird lung by presenting better separation of PE from PG, and of phos- a more complete analysis of lung phospholip phatidylserine (PS) from PI. Phospholipids ids (including DSPC) in the chick during were identified on TLC plates by comparision development. It also reports the distribution with standards after staining with iodine va- of DSPC in embryonic lung, liver, and yolk, por (solvent system I),or from UV fluorescence and in lavage and isolated lamellar bodies from after heating plates (1 h at 180°C, solvent breathing chickens. Finally, we have deter- system 11). Individual phospholipids were mined actual rates of biosynthesis of pul- scraped from TLC plates into glass-stoppered monary PC and DSPC early in incubation and tubes, and eluted at 55°C in ethanokhloro- LUNG PHOSPHOLIPIDS IN CHICK EMBRYO 73 form:water:acetic acid ( 100:30: 20: 2) (Biezen- prepared as previously described (Heath and ski, '64). Recoveries ranged from 95% to 99%. Jacobson, '76). The twice-washed pellet was di- Lipid phosphorous in individual phospholipids luted to 8.5 ml with homogenization buffer, and extract was determined according to Bart- one half layered onto 8.5 ml of 0.75 M sucrose, lett ('59)after digestion with 400 p1 of 72% per- 0.05 M Tris-Hcl, pH 7.05, and centrifuged at chloric acid for 1 h at 220°C. Saturated 90,OOOg for 2.8h. The material located at the phospholipids were isolated according to the 0.25-0.75 M sucrose interface was collected, procedure of Mason et al. ('76).Approximately diluted to 10 ml with homogenization buffer, 1 mg of lipid was reacted with 500 pl of 6.2 and centrifuged at 10,OOOg for 30 min. The mg/ml OsO, in CCL; saturated neutral and resulting pellet was resuspended in 8 ml of phospholipids were separated using column 0.154 M KCl and centrifuged at 20,OOOg for 30 chromatography (neutral alumina; BioRad, min. Portions of this final pellet (lamellar AG7,lOO-200 mesh). Saturated phospholipids bodies), as well as the more dense pellet ob- were further separated by TLC using solvent tained by centrifugation at 9O,OOOg, were fixed system 11. Recovery of DL-a-dipalmitoyl phos- for electron microscopy. The remaining mater- phatidylcholine standard (Sigma)from column ial was frozen at - 25 "C and analyzed for lipids and thin-layer chromatography was 96-98%.
Load more

Recommended publications
  • Glucocorticoids Accelerate Fetal Maturation of the Epidermal Permeability Barrier in the Rat
    Glucocorticoids accelerate fetal maturation of the epidermal permeability barrier in the rat. M Aszterbaum, … , G K Menon, M L Williams J Clin Invest. 1993;91(6):2703-2708. https://doi.org/10.1172/JCI116509. Research Article The cutaneous permeability barrier to systemic water loss is mediated by hydrophobic lipids forming membrane bilayers within the intercellular domains of the stratum corneum (SC). The barrier emerges during day 20 of gestation in the fetal rat and is correlated with increasing SC thickness and increasing SC lipid content, the appearance of well-formed lamellar bodies in the epidermis, and the presence of lamellar unit structures throughout the SC. Because glucocorticoids accelerate lung lamellar body and surfactant maturation in man and experimental animals, these studies were undertaken to determine whether maternal glucocorticoid treatment accelerates maturation of the epidermal lamellar body secretory system. Maternal rats were injected with betamethasone or saline (control) on days 16-18, and pups were delivered prematurely on day 19. Whereas control pups exhibited immature barriers to transepidermal water loss (8.16 +/- 0.52 mg/cm2 per h), glucocorticoid-treated pups exhibited competent barriers (0.74 +/- 0.14 mg/cm2 per h; P < 0.001). Glucocorticoid treatment also: (a) accelerated maturation of lamellar body and SC membrane ultrastructure; (b) increased SC total lipid content twofold; and (c) increased cholesterol and polar ceramide content three- to sixfold. Thus, glucocorticoids accelerate the functional, morphological, and lipid biochemical maturation of the permeability barrier in the fetal rat. Find the latest version: https://jci.me/116509/pdf Glucocorticoids Accelerate Fetal Maturation of the Epidermal Permeability Barrier in the Rat Michelle Aszterbaum, * Kenneth R.
    [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]
  • Electronic Cigarettes Disrupt Lung Lipid Homeostasis and Innate Immunity Independent of Nicotine
    Electronic cigarettes disrupt lung lipid homeostasis and innate immunity independent of nicotine Matthew C. Madison, … , David B. Corry, Farrah Kheradmand J Clin Invest. 2019. https://doi.org/10.1172/JCI128531. Research Article Immunology Inflammation Electronic nicotine delivery systems (ENDS) or e-cigarettes have emerged as a popular recreational tool among adolescents and adults. Although the use of ENDS is often promoted as a safer alternative to conventional cigarettes, few comprehensive studies have assessed the long-term effects of vaporized nicotine and its associated solvents, propylene glycol (PG) and vegetable glycerin (VG). Here, we show that compared with smoke exposure, mice receiving ENDS vapor for 4 months failed to develop pulmonary inflammation or emphysema. However, ENDS exposure, independent of nicotine, altered lung lipid homeostasis in alveolar macrophages and epithelial cells. Comprehensive lipidomic and structural analyses of the lungs revealed aberrant phospholipids in alveolar macrophages and increased surfactant-associated phospholipids in the airway. In addition to ENDS-induced lipid deposition, chronic ENDS vapor exposure downregulated innate immunity against viral pathogens in resident macrophages. Moreover, independent of nicotine, ENDS-exposed mice infected with influenza demonstrated enhanced lung inflammation and tissue damage. Together, our findings reveal that chronic e-cigarette vapor aberrantly alters the physiology of lung epithelial cells and resident immune cells and promotes poor response to infectious challenge. Notably, alterations in lipid homeostasis and immune impairment are independent of nicotine, thereby warranting more extensive investigations of the vehicle solvents used in e-cigarettes. Find the latest version: http://jci.me/128531/pdf The Journal of Clinical Investigation RESEARCH ARTICLE Electronic cigarettes disrupt lung lipid homeostasis and innate immunity independent of nicotine Matthew C.
    [Show full text]
  • The Epidermal Lamellar Body: a Fascinating Secretory Organelle
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE See relatedprovided article by Elsevier on page- Publisher 1137 Connector The Epidermal Lamellar Body: A Fascinating Secretory Organelle Manige´ Fartasch Department of Dermatology, University of Erlangen, Germany The topic of the function and formation of the epidermal LAMP-1. Instead, it expresses caveolin—a cholesterol- permeability barrier continue to be an important issue to binding scaffold protein that facilitates the assembly of understand regulation and development of the normal and cholesterol—and sphingolipids into localized membrane abnormal epidermis. A major player in the formation of the domains or ‘‘rafts’’ (Sando et al, 2003), which typically serve barrier, i.e., the stratum corneum (SC), is a tubular and/or as targets for apical transport of vesicles of Golgi origin. To ovoid-shaped membrane-bound organelle that is unique to date, a large body of evidence supports the concept that mammalian epidermis. In the past, this organelle has been LB, which shows morphology ranging from vesicles to embellished largely with descriptive names attributed to tubules on EM, are probably products of the tubulo- its perceived functional properties like membrane coating vesicular elements of the trans-Golgi network (TGN) that granule, keratinosome, cementsoms, and lamellar body/ is a tubulated sorting and delivery portion of the Golgi granule (LB). Over the last decade, data from several apparatus (Elias et al, 1998; Madison, 2003). Recently, laboratories documented
    [Show full text]
  • 2 Current Knowledge Status of the Stratum Corneum Structure and Transdermal Permeation Enhancement
    2. CURRENT KNOWLEDGE STATUS 2 Current knowledge status of the stratum corneum structure and transdermal permeation enhancement 2.1 The organization of the mammalian skin The skin consists of three distinct layers [2, 8]. The subcutis and the dermis , forming the bulk of skin, are made up of adipose and connective tissue elements, respectively. The overlying, avascular epidermis is composed primarily of keratinocytes and is divisible into four layers, namely the stratum basale, spinosum, granulosum, and corneum [2]. These layers present different stages of the cell differentiation, termed keratinisation . The continuously dividing stem cells on the basal layer generate columns of keratinocytes, which finally differentiate into the flattened corneocytes (Fig. 2.1). The innermost epidermal layer, the stratum basale, is a single layer of columnar basal cells that remain attached to the basement membrane via hemidesmosomes. The next epidermal layer, the stratum spinosum , has a spiny appearance of its cells in histological sections due to the abundance of desmosomes. First in this layer, lamellar bodies (also called membrane coating granules, keratinosomes or Odland bodies) and increased amount of keratin filaments can be detected. In the stratum granulosum , a quantitative increase in keratin synthesis occurs. The keratohyalin granules containing proteins (profillaggrin, loricrin and keratin) become progressively larger and give the name to this layer. Simultaneously, the uppermost cells in the stratum granulosum display a unique structural and functional organization of the lamellar bodies consistent with their readiness to terminally differentiate into a corneocyte, during which the lamellar bodies are secreted to the intercellular domains. The uppermost layer of the epidermis, the SC, creates the main skin barrier.
    [Show full text]
  • Degradation of Dipalmitoyl Phosphatidylcholine by Isolated Rat
    Degradation of Dipalmitoyl Phosphatidylcholine by Isolated Rat Granular Pneumocytes and Reutilization for Surfactant Synthesis Avinash Chander, Jayne Reicherter, and Aron B. Fisher Institutefor Environmental Medicine, University ofPennsylvania School ofMedicine, Philadelphia, Pennsylvania 19104-6068 Abstract biosynthesized surfactant (8, 9). Another pathway of surfactant clearance by lung tissue has been elucidated in recent years. In We investigated metabolic utilization of exogenous (modelled vivo studies on instillation of biosynthesized surfactant (9-1 1) after lung surfactant) phospholipids by granular pneumocytes or liposomes prepared from synthetic lipids (1 1, 12) have sug- in primary culture. Cells were incubated for 21, 65, and 140 min gested involvement of granular pneumocytes in this process. with pH-methylldipalmitoylphosphatidylcholine (DPPC) con- Using these cells in primary culture, we have previously shown taining liposomes prepared from synthetic lipids. Radioactivity that they internalize exogenous phospholipids and that this up- in cellular phosphatidylcholine (PC) declined steadily to 50% of take is dependent upon concentration of phospholipids, the time the total trypsin-resistant cell-associated radioactivity. The pro- and temperature of incubation, and can be modulated by met- portion of radioactivity increased with time in cytidine-5'-di- abolic inhibitors (13). In this report we extend our investigation phosphate-choline and phosphorylcholine, which suggested re- to localize the phosphatidylcholine (PC) radioactivity in sub- utilization of choline for PC synthesis. Cells incubated with li- cellular fractions and provide evidence for resynthesis of PC posomes for 2 h revealed that of the total cell-associated from degradation products. radioactivity, 7% was in lamellar bodies and 10% in the micro- somal fraction. The lipid-associated radioactivity was 24% in Methods "soluble," 96% in lamellar bodies, and 92% in the microsomal fraction.
    [Show full text]
  • SFTPB Gene Surfactant Protein B
    SFTPB gene surfactant protein B Normal Function The SFTPB gene provides instructions for making a protein called surfactant protein-B ( SP-B). This protein is one of four proteins (each produced from a different gene) in surfactant, a mixture of certain fats (called phospholipids) and proteins that lines the lung tissue and makes breathing easy. Without normal surfactant, the tissue surrounding the air sacs in the lungs (the alveoli) sticks together after exhalation ( because of a force called surface tension), causing the alveoli to collapse. As a result, filling the lungs with air on each breath becomes very difficult, and the delivery of oxygen to the body is impaired. Surfactant lowers surface tension, easing breathing and avoiding lung collapse. The SP-B protein helps spread the surfactant across the surface of the lung tissue, aiding in the surface tension-lowering property of surfactant. The phospholipids and proteins that make up surfactant are packaged in cellular structures known as lamellar bodies, which are found in specialized lung cells. The surfactant proteins must go through several processing steps to mature and become functional; some of these steps occur in lamellar bodies. The SP-B protein plays a role in the formation of lamellar bodies and, thus, affects the processing of a surfactant protein called surfactant protein-C (SP-C). Health Conditions Related to Genetic Changes Surfactant dysfunction More than 30 mutations in the SFTPB gene that cause surfactant dysfunction have been identified. Surfactant dysfunction due to SFTPB gene mutations (often called SP-B deficiency) causes severe, often fatal breathing problems in newborns.
    [Show full text]
  • Surfactant Dysfunction
    Surfactant dysfunction Description Surfactant dysfunction is a lung disorder that causes breathing problems. This condition results from abnormalities in the composition or function of surfactant, a mixture of certain fats (called phospholipids) and proteins that lines the lung tissue and makes breathing easy. Without normal surfactant, the tissue surrounding the air sacs in the lungs (the alveoli) sticks together (because of a force called surface tension) after exhalation, causing the alveoli to collapse. As a result, filling the lungs with air on each breath becomes very difficult, and the delivery of oxygen to the body is impaired. The signs and symptoms of surfactant dysfunction can vary in severity. The most severe form of this condition causes respiratory distress syndrome in newborns. Affected babies have extreme difficulty breathing and are unable to get enough oxygen. The lack of oxygen can damage the baby's brain and other organs. This syndrome leads to respiratory failure, and most babies with this form of the condition do not survive more than a few months. Less severe forms of surfactant dysfunction cause gradual onset of breathing problems in children or adults. Signs and symptoms of these milder forms are abnormally rapid breathing (tachypnea); low concentrations of oxygen in the blood (hypoxemia); and an inability to grow or gain weight at the expected rate (failure to thrive). There are several types of surfactant dysfunction, which are identified by the genetic cause of the condition. One type, called SP-B deficiency, causes respiratory distress syndrome in newborns. Other types, known as SP-C dysfunction and ABCA3 deficiency, have signs and symptoms that range from mild to severe.
    [Show full text]
  • Altered Lamellar Body Secretion and Stratum Corneum
    OBSERVATION Altered Lamellar Body Secretion and Stratum Corneum Membrane Structure in Netherton Syndrome Differentiation From Other Infantile Erythrodermas and Pathogenic Implications Manige´ Fartasch, MD; Mary L. Williams, MD; Peter M. Elias, MD Background: The infant with Netherton syndrome (NS) tum corneum layer was largely replaced by parakera- typically displays a generalized erythroderma covered by totic cells. A distinctive feature—premature secretion of fine, translucent scales, which can be difficult to distin- lamellar body contents—occurred only in NS. Further- guish clinically from erythrodermic psoriasis, nonbul- more, lamellar body–derived extracellular lamellae and lous congenital ichthyosiform erythroderma, or other in- stratum corneum lipid membranes were separated ex- fantile erythrodermas. Some infants with NS develop tensively by foci of electron-dense material. Finally, trans- progressive hypernatremic dehydration, failure to thrive, formation of lamellar body–derived lamellae into ma- and enteropathy. Such complications can be fatal. Diag- ture lamellar membrane structures was disturbed in NS. nosis is typically delayed until the appearance of a pa- thognomonic hair shaft anomaly, trichorrhexis invagi- Conclusions: Premature lamellar body secretion and foci nata (bamboo hair). To facilitate the early diagnosis of of electron-dense material in the intercellular spaces of NS, we obtained biopsy specimens from 7 patients with stratum corneum, features not observed in other eryth- erythrodermic NS and compared their morphologic find- rodermic disorders, appear to be frequent and relatively ings to those of 3 patients with erythrodermic psoriasis specific markers for NS. These ultrastructural features and 2 with congenital ichthyosiform erythroderma. Bi- could permit the early diagnosis of NS before the appear- opsy specimens were processed for light and electron mi- ance of the hair shaft abnormality.
    [Show full text]
  • Hydroxychloroquine, a Successful
    Shaaban et al. J Med Case Reports (2021) 15:54 https://doi.org/10.1186/s13256-020-02604-5 CASE REPORT Open Access Hydroxychloroquine, a successful treatment for lung disease in ABCA3 defciency gene mutation: a case report Waleed Shaaban1, Majeda Hammoud2*, Ali Abdulraheem1, Yasser Yahia Elsayed1 and Nawal Alkazemi1 Abstract Background: Pulmonary surfactant is a complex mixture of lipids and specifc proteins that stabilizes the alveoli at the end of expiration. Mutations in the gene coding for the triphosphate binding cassette transporter A3 (ABCA3), which facilitates the transfer of lipids to lamellar bodies, constitute the most frequent genetic cause of severe neona- tal respiratory distress syndrome and chronic interstitial lung disease in children. Hydroxychloroquine can be used as an efective treatment for this rare severe condition. Case presentation: We report a late preterm Bosnian baby boy (36 weeks) who sufered from a severe form of res- piratory distress syndrome with poor response to intensive conventional management and whole exome sequencing revealed homozygous ABCA3 mis-sense mutation. The baby showed remarkable improvement of the respiratory con- dition after the initiation of Hydroxychloroquine, Azithromycin and Corticosteroids with the continuation of Hydroxy- chloroquine as a monotherapy till after discharge from the hospital. Conclusion: Outcome in patients with ABCA3 mutations is variable ranging from severe irreversible respiratory failure in early infancy to chronic interstitial lung disease in childhood (ChILD) usually with the need for lung trans- plantation in many patients surviving this rare disorder. Hydroxychloroquine through its anti-infammatory efects or alteration of intra-cellular metabolism may have an efect in treating cases of ABCA3 gene mutations.
    [Show full text]
  • Membrane Architecture of Pulmonary Lamellar Bodies Revealed by Post-Correlation On-Lamella Cryo-CLEM
    bioRxiv preprint doi: https://doi.org/10.1101/2020.02.27.966739; this version posted February 27, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Membrane architecture of pulmonary lamellar bodies revealed by post-correlation on-lamella cryo-CLEM Steffen Klein1,#, Benedikt H. Wimmer1,#, Sophie L. Winter1, Androniki Kolovou1, Vibor Laketa2, Petr Chlanda1,* 1) Membrane Biology of Viral Infection Group, Center for Integrative Infectious Diseases, University Hospital Heidelberg 2) Infectious Diseases Imaging Platform (IDIP), Center for Integrative Infectious Diseases, University Hospital Heidelberg # equal contribution *correspondence to: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.02.27.966739; this version posted February 27, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Abstract Lamellar bodies (LBs) are surfactant rich organelles in alveolar type 2 cells. LBs disassemble into a lipid-protein network that reduces surface tension and facilitates gas exchange at the air-water interface in the alveolar cavity. Current knowledge of LB architecture is predominantly based on electron microscopy studies using disruptive sample preparation methods. We established a post-correlation on-lamella cryo-correlative light and electron microscopy approach for cryo-FIB milled lung cells to structurally characterize and validate LB identity in their unperturbed state using the well-established ABCA3-eGFP marker. In situ cryo-electron tomography revealed that LBs are composed of lipidic structures unique in organelle biology.
    [Show full text]
  • VPS33B and VIPAR Are Essential for Epidermal Lamellar Body Biogenesis
    BBA - Molecular Basis of Disease 1864 (2018) 1609–1621 Contents lists available at ScienceDirect BBA - Molecular Basis of Disease journal homepage: www.elsevier.com/locate/bbadis VPS33B and VIPAR are essential for epidermal lamellar body biogenesis and T function ⁎ Clare Rogersona,b, ,1, Paul Gissena,b,c a MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK b Institute of Child Health, University College London, London WC1N 1EH, UK c Inherited Metabolic Diseases Unit, Great Ormond Street Hospital, London WC1N 3JH, UK ARTICLE INFO ABSTRACT Keywords: Mutations in VPS33B and VIPAS39 cause the severe multisystem disorder Arthrogryposis, Renal dysfunction and ARC syndrome Cholestasis (ARC) syndrome. Amongst other symptoms, patients with ARC syndrome suffer from severe ich- ARKID syndrome thyosis. Roles for VPS33B and VIPAR have been reported in lysosome-related organelle biogenesis, integrin CHEVI complex recycling, collagen homeostasis and maintenance of cell polarity. Mouse knockouts of Vps33b or Vipas39 are Lamellar bodies good models of ARC syndrome and develop an ichthyotic phenotype. We demonstrate that the skin manifes- VIPAR tations in Vps33b and Vipar deficient mice are histologically similar to those of patients with ARC syndrome. VPS33B Histological, immunofluorescent and electron microscopic analysis of Vps33b and Vipar deficient mouse skin biopsies and isolated primary cells showed that epidermal lamellar bodies, which are essential for skin barrier function, had abnormal morphology and the localisation of lamellar body cargo was disrupted. Stratum corneum formation was affected, with increased corneocyte thickness, decreased thickness of the cornified envelope and reduced deposition of lipids. These defects impact epidermal homeostasis and lead to abnormal barrier forma- tion causing the skin phenotype in Vps33b and Vipar deficient mice and patients with ARC syndrome.
    [Show full text]