caa a22 4500 475773950 CHVBK 20180406123625.0 cr unu---uuuuu 170329e20000701xx s 000 0 eng 10.1007/s004180000157 doi (NATIONALLICENCE)springer-10.1007/s004180000157 Alveolar epithelial typeII cell apoptosis in vivo during resolution of keratinocyte growth factor-induced hyperplasia in the rat [Elektronische Daten] [Heinz Fehrenbach, Michael Kasper, Roland Koslowski, Tianli Pan, Dieter Schuh, Martin Müller, Robert J. Mason] Abstract.: Keratinocyte growth factor (KGF) induces rapid and transient hyperplasia of alveolar epithelial typeII 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 5mg KGF/kg body weight or diluent. Lungs were fixed 1, 2, 3, 5, and 7days later. Apoptosis was identified by TdT-mediated dUTP nick-end labeling (TUNEL), double-labeling for TUNEL and the typeII 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. TypeII cells exhibited Fas, FasL, Bcl-2, and procaspase-3 irrespective of treatment and time. Immunoelectron microscopy revealed Fas at the apical typeII cell membrane. Bax staining was prominent in controls (45-95% of typeII cell surface fraction), markedly decreased during hyperplasia at days2 (20-40%) and 3 (0-10%), and reappeared at day7 (25-45%) when apoptosis was prominent. Remnants of apoptotic typeII cells were incorporated in membrane-bound vacuoles of typeII cell neighbors as well as alveolar macrophages. The results indicate that typeII cells can enter the Fas/FasL/caspase-3 pathway regulated by Bax and Bcl-2. High Bcl-2:Bax levels favor typeII cell survival and a low rate of apoptosis during hyperplasia. Low Bcl-2:Bax levels favor typeII 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. Springer-Verlag, 2000 Keratinocyte growth factor Alveolar epithelium TypeII cell Hyperplasia Apoptosis Fas Fas ligand Bax Bcl-2 Caspase-3 nationallicence Fehrenbach Heinz Institute of Pathology, University Clinic "Carl Gustav Carus", TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany aut Kasper Michael Institute of Anatomy, Medical Faculty, TU Dresden, Germany aut Koslowski Roland Institute of Physiological Chemistry, Medical Faculty, TU Dresden, Germany aut Pan Tianli National Jewish Medical and Research Center, Denver, CO, USA aut Schuh Dieter Institute of Pathology, University Clinic "Carl Gustav Carus", TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany aut Müller Martin Institute of Pathology, University Clinic "Carl Gustav Carus", TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany aut Mason Robert J. National Jewish Medical and Research Center, Denver, CO, USA aut https://doi.org/10.1007/s004180000157 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s004180000157 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fehrenbach Heinz Institute of Pathology, University Clinic "Carl Gustav Carus", TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany aut NATIONALLICENCE 700 1- Kasper Michael Institute of Anatomy, Medical Faculty, TU Dresden, Germany aut NATIONALLICENCE 700 1- Koslowski Roland Institute of Physiological Chemistry, Medical Faculty, TU Dresden, Germany aut NATIONALLICENCE 700 1- Pan Tianli National Jewish Medical and Research Center, Denver, CO, USA aut NATIONALLICENCE 700 1- Schuh Dieter Institute of Pathology, University Clinic "Carl Gustav Carus", TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany aut NATIONALLICENCE 700 1- Müller Martin Institute of Pathology, University Clinic "Carl Gustav Carus", TU Dresden, Fetscherstrasse 74, 01307 Dresden, Germany aut NATIONALLICENCE 700 1- Mason Robert J. National Jewish Medical and Research Center, Denver, CO, USA aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer