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  • 1
    ISSN: 1432-119X
    Keywords: Keratinocyte growth factor Alveolar epithelium Type II cell Hyperplasia Apoptosis Fas Fas ligand Bax Bcl-2 Caspase-3
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract. Keratinocyte growth factor (KGF) induces rapid and transient hyperplasia of alveolar epithelial type II cells. We sought to determine components of the apoptotic process involved in the resolution of this hyperplasia and the fate of the apoptotic cells. Rats received intrabronchial instillation of 5 mg KGF/kg body weight or diluent. Lungs were fixed 1, 2, 3, 5, and 7 days later. Apoptosis was identified by TdT-mediated dUTP nick-end labeling (TUNEL), double-labeling for TUNEL and the type II cell marker MNF116, and electron microscopy. Fas, FasL, Bax, Bcl-2, and pro- and active caspase-3 were studied by immunohistochemistry. Changes were quantified by stereology. Cell type specificity was investigated by immunofluorescence double staining. Type II cells exhibited Fas, FasL, Bcl-2, and procaspase-3 irrespective of treatment and time. Immunoelectron microscopy revealed Fas at the apical type II cell membrane. Bax staining was prominent in controls (45–95% of type II cell surface fraction), markedly decreased during hyperplasia at days 2 (20–40%) and 3 (0–10%), and reappeared at day 7 (25–45%) when apoptosis was prominent. Remnants of apoptotic type II cells were incorporated in membrane-bound vacuoles of type II cell neighbors as well as alveolar macrophages. The results indicate that type II cells can enter the Fas/FasL/caspase-3 pathway regulated by Bax and Bcl-2. High Bcl-2:Bax levels favor type II cell survival and a low rate of apoptosis during hyperplasia. Low Bcl-2:Bax levels favor type II cell apoptosis during resolution. Because of time-dependent changes that occur within a short time, the KGF-treated rat lung provides a useful in vivo model to investigate apoptosis in the context of tissue remodeling and repair.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0003-276X
    Keywords: Human lung ; Type II pneumocytes ; Lamellar bodies ; Surfactant ; Electron microscopy ; Morphometry ; Organ preservation ; Euro Collins solution ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Background: Pulmonary type II pneumocytes have been examined by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and morphometry in numerous mammals. Until now, the fine structure of the human type II pneumocyte has not been studied by means of morphometry.Methods: Eleven human donor lungs, which could not be made available for a suitable recipient, were preserved with Euro Collins solution (ECS) according to clinical organ preservation techniques. The lungs were fixed via the airways. Systematic random samples were analyzed by SEM, TEM, and classical stereological methods.Results: Type II pneumocytes showed normal fine structural characteristics. Morphometry revealed that although inter-individual variation due to some oedematous swelling was present, the cells were in a normal size range as indicated by an estimated mean volume of 763 ± 64 μm3. The volume densities were: nucleus 21.9 ± 2.2%, mitochondria 5.8 ± 0.9%, lamellar bodies 9.8 ± 3.6%, and remaining cytoplasmic components 62.4 ± 2.9% of the cell volume. Since the inter-individual variations in the volume densities referred to the cell may, to variable degrees, reflect the variation in the reference space, the volume densities referred to the constant test point system and the respective volume-to-surface ratios were used for interindividual comparisons. These parameters indicate that lamellar bodies were independent of cellular swelling, while mitochondria nucleus remaining cytoplasmic components increased in size with increasing cell size.Conclusions: Two to 7.5 hours of cold ischemia following ECS preservation do not deteriorate the fine structure of type II pneumocytes of human donor lungs. For reliable assessment of fine structural variation, morphometric parameters are required that are independent of variations in cell size. © 1995 Wiley-Liss, Inc.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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