title: Bromodeoxyuridine (BrdU)-label-retaining cells in mouse terminal bronchioles.
abstract: Adult male mice were continuously treated with bromodeoxyuridine (BrdU) for 1, 2, or 4 weeks by an osmotic pump. To detect BrdU-label-retaining cells (LRCs), putative progenitor/stem cells, other animals were continuously treated with BrdU for 2 weeks, and were then kept without any treatments for 2, 6, or 18 months. The lungs were fixed with 4% paraformaldehyde, and were paraffin-embedded. We observed terminal bronchioles with BrdU immunostaining alone or with BrdU immunostaining accompanying immunostaining for Clara cell secretory protein (CCSP), forkhead box protein J1 (FoxJ1), or calcitonin gene-related peptide (CGRP). The average incidences of BrdU-incorporated cells in the terminal bronchioles after 1, 2, and 4 weeks of continuous BrdU infusion were 6.2%, 11.9%, and 23.1%, respectively. Most BrdU-incorporated cells in these periods were CCSP-immunoreactive (91.7%, 91.3%, and 88.2%, respectively), which means progenitor function of Clara cells. FoxJ1-immunoreactive BrdU-incorporated cells were fewer (5.4%, 3.0%, 2.7%, respectively). The average incidences of BrdU-LRCs in the terminal bronchioles after 2, 6, and 18 months were 7.2%, 4.3, and 2.7%, respectively. Most BrdU-LRCs were CCSP-immunoreactive (91.0%, 92.7%, and 89.6%, respectively), and FoxJ1-immunoreactive BrdU-LRCs were fewer (6.0%, 5.7%, and 2.1%, respectively). CGRP-positive BrdU-incorporated cells were occasional. CGRP-positive BrdU-LRCs were detected in 17.6% of neuroepithelial bodies (NEBs) at 2 months, but disappeared at 6 months. BrdU-positive stem cell candidates, which locate at the brochiolo-alveolar duct junction or cover NEB, were few throughout this study. In conclusion, in the lungs treated only with BrdU, CCSP-immunoreactive cells are important to maintain homeostasis in the terminal bronchiolar epithelium.
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Medical Sciences, and Division of Pathology, Kumamoto Health Science University, Kumamoto, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kameyama
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Kudoh
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto, and Division of Diagnostic Surgical Pathology, Yokohama City University Hospital, Yokohama, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Udaka
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Kagayama
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto, and Department of Pathology, Faculty of Medicine, Suez Canal University, Egypt.
authors.forename: Wael
authors.initials: W
authors.lastname: Hassan
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Kohki
authors.initials: K
authors.lastname: Hasegawa
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Niimori-Kita
authors.affiliation: Department of Pathology and Experimental Medicine, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan. takaito@kumamoto-u.ac.jp.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ito
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D001973:Bromodeoxyuridine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055745:Bronchioles / Q000166:cytology* / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D046568:Neuroepithelial Bodies / Q000166:cytology / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism; D013997:Time Factors; D014598:Uteroglobin / Q000378:metabolism
chemical_list: C481963:FOXJ1 protein, mouse; D051858:Forkhead Transcription Factors; D014598:Uteroglobin; D001973:Bromodeoxyuridine; D015740:Calcitonin Gene-Related Peptide