Linking progression of fibrotic lung remodeling and ultrastructural alterations of alveolar epithelial type II cells in the amiodarone mouse model

被引:30
|
作者
Birkelbach, Bastian [1 ,2 ]
Lutz, Dennis [1 ,2 ]
Ruppert, Clemens [3 ]
Henneke, Ingrid [3 ]
Lopez-Rodriguez, Elena [1 ,2 ]
Guenther, Andreas [3 ,4 ,5 ,6 ]
Ochs, Matthias [1 ,2 ,7 ]
Mahavadi, Poornima [3 ]
Knudsen, Lars [1 ,2 ]
机构
[1] Hannover Med Sch, Inst Funct & Appl Anat, D-30625 Hannover, Germany
[2] Biomed Res Endstage & Obstruct Lung Dis Hannover, Hannover, Germany
[3] Univ Giessen, Dept Internal Med, UGMLC, Giessen, Germany
[4] European IPF Network, Giessen, Germany
[5] Excellence Cluster Cardiopulm Syst ECCPS, Giessen, Germany
[6] Lung Clin Waldhof Elgershausen, Greifenstein, Germany
[7] REBIRTH Cluster Excellence, Hannover, Germany
关键词
stereology; pulmonary fibrosis; alveolar epithelial type II cells; surfactant; collapse induration; IDIOPATHIC PULMONARY-FIBROSIS; HERMANSKY-PUDLAK-SYNDROME; ENDOPLASMIC-RETICULUM STRESS; PROTEIN-C GENE; INTERSTITIAL PNEUMONIA; COMPUTED-TOMOGRAPHY; IN-VITRO; SURFACTANT; APOPTOSIS; TISSUE;
D O I
10.1152/ajplung.00279.2014
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Chronic injury of alveolar epithelial type II cells (AE2 cells) represents a key event in the development of lung fibrosis in animal models and in humans, such as idiopathic pulmonary fibrosis (IPF). Intratracheal delivery of amiodarone to mice results in a profound injury and macroautophagy-dependent apoptosis of AE2 cells. Increased autophagy manifested in AE2 cells by disturbances of the intracellular surfactant. Hence, we hypothesized that ultrastructural alterations of the intracellular surfactant pool are signs of epithelial stress correlating with the severity of fibrotic remodeling. With the use of design-based stereology, the amiodarone model of pulmonary fibrosis in mice was characterized at the light and ultrastructural level during progression. Mean volume of AE2 cells, volume of lamellar bodies per AE2 cell, and mean size of lamellar bodies were correlated to structural parameters reflecting severity of fibrosis like collagen content. Within 2 wk amiodarone leads to an increase in septal wall thickness and a decrease in alveolar numbers due to irreversible alveolar collapse associated with alveolar surfactant dysfunction. Progressive hypertrophy of AE2 cells and increase in mean individual size and total volume of lamellar bodies per AE2 cell were observed. A high positive correlation of these AE2 cell-related ultrastructural changes and the deposition of collagen fibrils within septal walls were established. Qualitatively, similar alterations could be found in IPF samples with mild to moderate fibrosis. We conclude that ultrastructural alterations of AE2 cells including the surfactant system are tightly correlated with the progression of fibrotic remodeling.
引用
收藏
页码:L63 / L75
页数:13
相关论文
共 50 条
  • [41] ISOLATION OF NONCILIATED BRONCHIOLAR EPITHELIAL (CLARA) CELLS AND ALVEOLAR TYPE-II CELLS FROM MOUSE LUNGS
    MASSEY, TE
    GEDDES, BA
    FORKERT, PG
    CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 1987, 65 (12) : 2368 - 2372
  • [42] Steroid metabolism in co-cultures of A/J mouse alveolar epithelial type II cells and Clara cells
    Hansen, T
    Borlak, J
    NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 2001, 363 (04) : R138 - R138
  • [43] Increased lung expansion alters the proportions of type I and type II alveolar epithelial cells in fetal sheep
    Flecknoe, S
    Harding, R
    Maritz, G
    Hooper, SB
    AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2000, 278 (06) : L1180 - L1185
  • [44] A pure population of lung alveolar epithelial type II cells derived from human embryonic stem cells
    Wang, Dachun
    Haviland, David L.
    Burns, Alan R.
    Zsigmond, Eva
    Wetsel, Rick A.
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (11) : 4449 - 4454
  • [45] Isolation and characterization of lung resident mesenchymal stem cells capable of differentiating into alveolar epithelial type II cells
    Gong, Xuemin
    Sun, Zhaorui
    Cui, Di
    Xu, Xiaomeng
    Zhu, Huiming
    Wang, Lihui
    Qian, Weiping
    Han, Xiaodong
    CELL BIOLOGY INTERNATIONAL, 2014, 38 (04) : 405 - 411
  • [47] Induction of type II alveolar epithelial cells apoptosis in mouse by lipopolysaccharide does not require TNF-α
    Song, Y
    Shi, Y
    Harken, AH
    Meng, XZ
    CHINESE MEDICAL JOURNAL, 2003, 116 (04) : 625 - 629
  • [48] Hyperplastic Alveolar Epithelial Type Ii Cells In Idiopathic Pulmonary Fibrosis Co-Express Markers Of Other Lung Epithelial Cells
    Liebler, J. M.
    Zhou, B.
    Flodby, P.
    Crandall, E.
    Borok, Z.
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2014, 189
  • [49] Xbp1 Deficiency In Type Ii Alveolar Epithelial Cells Protects Against Lung Fibrosis
    Brands, J.
    Bueno, M.
    Rojas, M.
    Mora, A. L.
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2016, 193
  • [50] Intratracheal Trasplantation Of Alveolar Type Ii Cells In An Experimental Model Of Acute Lung Injury
    Guillamat-Prats, R.
    Puig, F.
    Herrero, R.
    Serrano-Mollar, A.
    Camprubi-Rimblas, M.
    Chimenti, L.
    Tijero, J.
    Gomez, M. N.
    Blanch, L.
    Artigas, A.
    AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2015, 191