Neuroendocrine APUD Cells

Although immunohistochemical staining has been invaluable in defining the abundance of neuroendocrine cells in experimental and disease conditions. 

After naphthalene (300 mg/kg i.p.) treatment of mice and epithelial repair, neuroepithelial bodies were significantly increased along the walls of the airways as well as on branch point ridges (Peake et al. 2000). Reynolds et al. (2000) provided the following evidence that the neuroepithelial body microenvironment serves as a source of airway progenitor cells that contribute for focal regeneration of the airway epithelium  

AT-Diethylnitrosamine Hamster Rat Rabbit Reznik-Schuller (1976), Linnoila et al. (1984) Kleinerman et al. (1981) Huntrakoon et al. (1989), Hung et al. (1991) 

Groups of 40-50 neurone specific enolase immuno-reactive cells, forming microtumours, were seen in the epithelium of larger airways of rats exposed to asbestos fibres up to 3 years (Cole et al. 1982). 

Pulmonary neuroendocrine cell hyperplasia may result after carcinogen treatment in hamsters given supranormal oxygen (Sunday et al. 1994). 

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APUD cells are descended from an ancestral neuron although the axon has been lost, innervation is still possible via synaptic terminals, or nervous control may be indirect. Six modes of APUD cell expression are recognized neurocrine (into neurons), neuroendocrine (via axons), endocrine (into the blood stream), paracrine (into the intercellular space), epicrine (into somatic cells), and exocrine (to the exterior). 

The APUD concept of a diffuse neuroendocrine system has been defined as follows by A.G.E.Pearse [in Centrally Acting Peptides, J. Hughes (ed.), MacMillan, 1978] The cells of the APUD series, producing peptides active as hormones or as neurotransmitters, are all derived from neuroendocrine-programed cells originating from the ectoblast. They constitute a third (endocrine or neuroendocrine) division of the nervous system whose cells act as third line effectors to support, modulate or amplify the action of neurons in the somatic and autonomic divisions, and possibly as tropins to both neuronal and non-neuronal cells . 

A great deal of work using LeDouarin s method proved that C cells of the thyroid gland and of the ultimobranchial body, type 1 cells of the carotid body, and adrenal medullary N and NA cells are derived from the neural crest. Pearse admitted that the APUD cells of the stomach, intestine, and pancreas are beyond doubt not derived from the neural crest. Instead, they come from neuroendocrine programmed ectoblast. ... 

NET cells are characterized by their ability to take up and concentrate amine precursors such as dihydroxy-phenylalanine (DOPA) and hydroxytryptophane (HTP) and to produce amines and peptides, for which reason they were also classified as amine precursor uptake and decarboxylation (APUD) cells. They may also express different peptide hormone receptors (like somatostatin receptors) or transporters at their cell membrane. These uptake mechanisms and the presence of peptide receptors and transporters constitute the basis for the use of specific radiolabeled ligands for imaging of neuroendocrine tumors. 

Enolase is a glycolytic enzyme also known as phosphopyru-vate hydratase. Neuron-specific enolase (NSE) is the form of enolase found in neuronal tissue and in the cells of the diffuse neuroendocrine system and the amine precursor uptake, and decarboxylation (APUD) tissue. NSE is found in tumors associated with the neuroendocrine origin, including small cell lung cancer (SCLC), neuroblastoma, pheochromocytoma, carcinoid, medullary carcinoma of the thyroid, melanoma, and pancreatic endocrine tumors. 

Endocrine-like cells with biochemical characteristics of Amine Precursor Uptake and Decaboxylase (APUD) were quantified in the tracheal, bronchial, and bronchiolar epithelia of the guinea pig by four histochemical stains Grimelius, en-block silver, lead-haematoxylin-en block silver and periodic acid-Schiff-lead haematoxylin (Marchevsky et al. 1983). There were significant differences between the number of epithelial cells in the various locales of the respiratory tree 318 5.63 epithelial cells/ mm in the trachea, 263 17.11 epithelial cells/mm in the bronchi and 193 4.21 epithelial cells/mm in the bronchioles. Boers et al. (1996) did not find any difference in the number of neuroendocrine cells between large (airway diameter >4.5 mm) and small (airway diameter <1.2 mm) conducting airways in 9 human subjects without pulmonary disease out of 250 autopsy cases. 

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