ABSTRACT
Pulmonary neuroendocrine cells (PNECs) have crucial roles in airway physiology and immunity by producing bioactive amines and neuropeptides (NPs). A variety of human diseases exhibit PNEC hyperplasia. Given accumulated evidence that PNECs represent a heterogenous population of cells, we investigate how PNECs differ, whether the heterogeneity is similarly present in mouse and human cells, and whether specific disease involves discrete PNECs. Herein, we identify three distinct types of PNECs in human and mouse airways based on single and double positivity for TUBB3 and the established NP markers. We show that the three PNEC types exhibit significant differences in NP expression, homeostatic turnover, and response to injury and disease. We provide evidence that these differences parallel their distinct cell of origin from basal stem cells (BSCs) or other airway epithelial progenitors.
Subject(s)
Cell Lineage/genetics , Epithelial Cells/pathology , Neuroendocrine Cells/pathology , Stem Cells/pathology , Tubulin/genetics , Animals , Basic Helix-Loop-Helix Transcription Factors/genetics , Basic Helix-Loop-Helix Transcription Factors/metabolism , Cell Differentiation , Epithelial Cells/classification , Epithelial Cells/metabolism , Female , Gene Expression Regulation , Humans , Hyperplasia/genetics , Hyperplasia/metabolism , Hyperplasia/pathology , Infant , Influenza A Virus, H1N1 Subtype/growth & development , Influenza A Virus, H1N1 Subtype/pathogenicity , Lung , Male , Mice , Mice, Transgenic , Neuroendocrine Cells/classification , Neuroendocrine Cells/metabolism , Neuropeptides/genetics , Neuropeptides/metabolism , Orthomyxoviridae Infections/genetics , Orthomyxoviridae Infections/metabolism , Orthomyxoviridae Infections/pathology , Orthomyxoviridae Infections/virology , Signal Transduction , Stem Cells/classification , Stem Cells/metabolism , Sudden Infant Death/genetics , Sudden Infant Death/pathology , Transcription Factors/genetics , Transcription Factors/metabolism , Tubulin/metabolism , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolismABSTRACT
Neuroendocrine neoplasms of the lung continue to undergo scrutiny, with respect to the diagnostic terminology recommended for them and details of their clinicopathologic profiles. This overview considers the nosological evolution of such lesions and presents current views on classification schemes that pertain to them.
Subject(s)
Lung Neoplasms/pathology , Neuroendocrine Cells/pathology , Neuroendocrine Tumors/pathology , Terminology as Topic , Apoptosis , Biomarkers, Tumor/analysis , Biopsy , Cell Proliferation , Humans , Immunohistochemistry , Lung Neoplasms/chemistry , Lung Neoplasms/classification , Necrosis , Neuroendocrine Cells/chemistry , Neuroendocrine Cells/classification , Neuroendocrine Tumors/chemistry , Neuroendocrine Tumors/classification , Predictive Value of Tests , Prognosis , Tomography, X-Ray ComputedABSTRACT
Glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide (GLP)-1 and GLP-2 are hormones secreted from specialized K cells (GIP) and L cells (GLP-1, GLP-2) in the intestinal mucosa. These hormones play major roles in health and disease by modulating insulin secretion, satiety, and multiple intestinal functions. The aim of this study was to describe the distribution of K cells and L cells in the intestines of healthy cats. Samples of duodenum, mid-jejunum, ileum, cecum, and colon were collected from 5 cats that were euthanized for reasons unrelated to this study and had no gross or histologic evidence of gastrointestinal disease. Samples stained with rabbit-anti-porcine GIP, mouse-anti-(all mammals) GLP-1, or rabbit-anti-(all mammals) GLP-2 antibodies were used to determine the number of cells in 15 randomly selected 400× microscopic fields. In contrast to other mammals (eg, dogs) in which K cells are not present in the ileum and aborally, GIP-expressing cells are abundant throughout the intestines in cats (>6/high-power field in the ileum). Cells expressing GLP-1 or GLP-2 were most abundant in the ileum (>9/high-power field) as in other mammals, but, although GLP-1-expressing cells were abundant throughout the intestines, GLP-2-expressing cells were rarely found in the duodenum. In conclusion, the distribution of GIP-secreting K cells in cats is different from the distribution of K cells that is described in other mammals. The difference in distribution of GLP-2- and GLP-1-expressing cells suggests that more than 1 distinct population of L cells is present in cats.
Subject(s)
Cats/anatomy & histology , Glucagon-Like Peptide 1/analysis , Intestines/cytology , Neuroendocrine Cells/cytology , Animals , Antibodies , Cecum/cytology , Colon/cytology , Duodenum/cytology , Female , Gastric Inhibitory Polypeptide/analysis , Gastric Inhibitory Polypeptide/immunology , Glucagon-Like Peptide 1/immunology , Glucagon-Like Peptide 2/analysis , Glucagon-Like Peptide 2/immunology , Ileum/cytology , Immunohistochemistry , Intestines/chemistry , Jejunum/cytology , Male , Mice , Neuroendocrine Cells/chemistry , Neuroendocrine Cells/classification , Rabbits , Species SpecificityABSTRACT
The complex clinico-morphological and immunohistochemical investigation of neuroendocrinal breast cancer has been carried out. Among 12 observations 3 histological types of neuroendocrinal breast cancer has been founded: parvicellular, colloid and clear-cell cancers. The questions of classification, therapeutic approach, collective and personal prognosis require the optimization of theirs clinico-morphological research with an immunohistochemical verification.
