title: Pulmonary neuroendocrine cell hyperplasia: identification, diagnostic criteria and incidence in untreated ageing rats of different strains.
abstract: Pulmonary Neuroendocrine Cells (PNEC) are found as clusters called neuroepithelial bodies (NEB) or as single cells scattered in the respiratory epithelium. Pulmonary neuroendocrine cell hyperplasia is recorded in humans and experimentally manipulated rodents. The objectives of this work were to identify the optimal immunohistochemical markers for PNEC in the rat for use on paraffin-embedded, formalin-fixed material and to provide the first comparative incidence of PNEC hyperplasia in untreated 2-year-old rats of different strains. Calcitonin-gene related peptide (CGRP) and protein G product 9.5 (PGP9.5) antibodies identified PNEC consistently and selectively. In contrast, PNEC did not express chromogranin-A or S-100. PNEC hyperplasia was defined as foci of PNEC with greater than 40 nuclei, excluding overlying respiratory epithelium and submucosal PNEC. PNEC hyperplasia was observed at low incidence (0-7%) in untreated 2-year-old Sprague-Dawley, Han Wistar and Wistar rats but not Fischer 344 rats. This is the first report of spontaneous PNEC hyperplasia in rats. The cause of this hyperplasia is unknown, but experimental models that induce PNEC hyperplasia by causing bronchiolar cell injury are discussed. PNEC neoplasia in the rat is unreported in the literature and was not observed in animals examined in this study.
authors.affiliation: Department of Pathology, Safety Asssessment, GlaxoSmithKline Research and Development Ltd, Herts, United Kingdom. richard.i.haworth@gsk.com
authors.forename: Richard
authors.initials: R
authors.lastname: Haworth
authors.forename: Jennie
authors.initials: J
authors.lastname: Woodfine
authors.forename: Sean
authors.initials: S
authors.lastname: McCawley
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Pilling
authors.forename: David J
authors.initials: DJ
authors.lastname: Lewis
authors.forename: Tom C
authors.initials: TC
authors.lastname: Williams
mesh_terms: D000375:Aging; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000032:analysis; D006965:Hyperplasia; D007150:Immunohistochemistry; D015994:Incidence; D008168:Lung / Q000473:pathology*; D009490:Neurosecretory Systems / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D043222:Ubiquitin Thiolesterase / Q000032:analysis
chemical_list: C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase; D015740:Calcitonin Gene-Related Peptide