Endocrine cell proliferation in the rat lung following asbestos inhalation

Johnson, Neil; Wagner, J. C.; Wills, Hope

doi:10.1007/bf02713725

Cited by 38 publications

(14 citation statements)

References 12 publications

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“…Multiple factors, including rates of neuropeptide synthesis, secretion, and degradation, as well as technical factors which are inherent to each of these two sampling methods, may account for this discrepancy (27) (27), and appears to cause NE cell hyperplasia if sustained (25,29). Asbestos fibers have been demonstrated to cause NE cell hyperplasia and increased bombesin-like immunoreactivity in an animal model (30,31), as has exposure to cigarette smoke (5). Several investigators have also demonstrated an independent proliferative effect on NE cells from nicotine (32) and nitrosamines (14,33 (34).…”

Section: Discussionmentioning

confidence: 99%

Increased pulmonary neuroendocrine cells with bombesin-like immunoreactivity in adult patients with eosinophilic granuloma.

Aguayo¹,

King²,

Waldron³

et al. 1990

J. Clin. Invest.

115

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IntroductionCigarette smoking is associated with hyperplasia of pulmonary neuroendocrine cells and variably increased levels of bombesin-like peptides in the lower respiratory tract. Because the neuropeptide bombesin is a chemoattractant for monocytes and a mitogen for 3T3 fibroblasts, we hypothesized that an excess of neuroendocrine cells and bombesin-like peptides could contribute to lung inflammation and fibrosis in certain cigarette smokers. Eosinophilic granuloma is a fibrotic lung disease of unknown etiology that in adults occurs almost invariably in cigarette smokers. We quantitated neuroendocrine cells with bombesin-like immunoreactivity in open lung biopsies from patients with eosinophilic granuloma (n = 6) and compared these with cigarette smokers (n = 6) who underwent lung resection for reasons other than primary lung disease. In addition, we compared them with patients with idiopathic pulmonary fibrosis (n = 8), a disease not associated with cigarette smoking. Finally, we also examined the mitogenic effect of bombesin on cultured human adult lung fibroblasts.The patients with eosinophilic granuloma exhibited a 10-fold increase in neuroendocrine cells with bombesin-like immunoreactivity compared to both smokers (P = 0.005) and patients with idiopathic pulmonary fibrosis (P = 0.005). In addition, bombesin produced a significant mitogenic effect on cultured human adult lung fibroblasts at concentrations of I nM and above. We conclude that increased numbers of pulmonary neuroendocrine cells with bombesin-like immunoreactivity are commonly found in patients with eosinophilic granuloma and, since bombesin-like peptides are chemotactic for monocytes and mitogenic for human lung fibroblasts, we speculate that neuroendocrine cell hyperplasia may be important in the pathogenesis of eosinophilic granuloma in adult cigarette smokers. (J. Clin. Invest. 1990. 86:838-844.)

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Section: Discussionmentioning

confidence: 99%

Increased pulmonary neuroendocrine cells with bombesin-like immunoreactivity in adult patients with eosinophilic granuloma.

Aguayo¹,

King²,

Waldron³

et al. 1990

J. Clin. Invest.

115

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“…Previous studies reported pulmonary PNEC and NEB hyperplasia in several experimental conditions in which the lung epithelial cells are exposed to inflammatory cytokines, chronic hypoxia, or a variety of toxic compounds. Interestingly, several groups (Johnson et al, 1980;Sheppard et al, 1982) reported that asbestos inhalation produces NE hyperplasia in rats. After quartz instillation in the present model, a very significant hyperplasia of NE cells was found in rat lungs, but it did not occur in mice and hamsters that underwent the same treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Either the total number of NEBs, the cell density of each NEB, or both are increased in lung inflammatory, fibrotic, or dysplastic conditions (Aguayo et al, 1990;Willett et al, 1999) or after the exposure to some toxic or carcinogenic products like nicotine or cigarette smoke (Aguayo, 1993), N-nitroso compounds (Huntrakoon et al, 1989;Sunday and Willett, 1992), or asbestos (Johnson et al, 1980;Sheppard et al, 1982). Cigarette smokers with NE hyperplasia have a greater risk of developing smokingrelated lung disease than smokers without NE hyperplasia (Aguayo, 1993).…”

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confidence: 99%

Hyperplasia of Alveolar Neuroendocrine Cells in Rat Lung Carcinogenesis by Silica with Selective Expression of Proadrenomedullin-Derived Peptides and Amidating Enzymes

Elizegi

Pino

Vicent

et al. 2001

Laboratory Investigation

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SUMMARY:Pulmonary neuroendocrine (NE) cells are found as clusters called neuroepithelial bodies (NEBs) or as single cells scattered in the respiratory epithelium. They express a variety of bioactive peptides, and they are thought to be the origin of NE lung tumors. Proadrenomedullin N-terminal 20 peptide (PAMP) is a peptide derived from the same precursor as adrenomedullin (AM). AM and PAMP are C-terminally amidated during their processing by a well-characterized amidating enzyme, peptidylglycine alpha-amidating monooxygenase (PAM). We explored AM, PAMP, and PAM expression as markers for NE hyperplasia in three rodent species (Fischer 344 rats, Syrian golden hamsters, and A/J mice) after a single intratracheal instillation of crystalline silica (quartz), which was previously found to induce different reactions in the three species. Rats developed a marked silicosis, with alveolar and bronchiolar hyperplasia and formation of peripheral lung epithelial tumors. Mice developed a moderate degree of silicosis, but not epithelial hyperplasia or tumors. Hamsters showed dust-storage lesions, but not silicosis or tumors. NE cells were immunolabeled for calcitonin gene-related peptide (CGRP), AM, PAMP, and PAM in serial sections of each lung. The numbers of positive NEBs per lung area and positive cells per NEB were quantified. A marked hyperplastic reaction in the NEBs of silica treated rats occurred only in alveolar NEBs, but not in bronchiolar NEBs. From Month 11 onwards, there were marked differences in the number of alveolar NEBs per section and in the number of cells per alveolar NEB immunoreactive for CGRP. No hyperplastic NE cell reaction was observed in silica-treated mice and hamsters. Significant PAMP and PAM expression was seen only in rat hyperplastic alveolar and in bronchiolar NEBs from Month 11 onwards. In E18, rat fetal lung NEBs were found to be strongly positive for PAMP and PAM. (Lab Invest 2001, 81:1627-1638.

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“…One result of pulmonary injury is fibrosis, and there is evidence that PECs might be involved in its pathogenesis [3][4][5][6][7][8]. In a previous study of 49 pairs of lungs affected by diffuse fibrosis at various stages of development, we could find no differences in the pulmonary endocrine system in comparison with control lungs, apart from a single focus of proliferation in an area affected by pneumonia [9].…”

mentioning

confidence: 85%

“…The contention that the products of PECs might play a role in pulmonary fibrogenesis arose as a result of observations from studies both of human [7,8,16,17] and animal [3,4] lungs, which described an association between endocrine cell proliferation and fibrosis, whether focal or diffuse. This idea was supported by studies of the function of the predominant secretory product of PECs, GRP, which showed it to be trophic not only to bronchial epithelium [18], but also pulmonary fibroblasts [19].…”

Section: Discussionmentioning

confidence: 99%

Pulmonary endocrine cells in anthracosilicotic lungs

Gosney

Peers²,

Beesley³

et al. 1997

Eur Respir J

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It has been suggested by some studies of human and animal lungs that the products of pulmonary endocrine cells, particularly gastrin-releasing peptide, might play a role in fibrogenesis, but more recent detailed studies of fibrotic human lungs have failed to confirm this. We have made a detailed quantitative examination of a series of fibrotic human lungs to see if we could determine whether there was any relationship between endocrine cells and fibrosis.Using immunocytochemistry, we investigated the morphology, content, distribution and number of pulmonary endocrine cells in 15 pairs of fibrotic lungs from coal miners, and compared their features with those of equivalent cells in agematched controls.Proliferation of endocrine cells was seen in the lungs of just two miners, in which it was focal and associated with acute bronchitis and bronchopneumonia. There was no difference between the miners and controls in the appearance (mostly solitary cells), content (predominantly gastrin-releasing peptide and calcitonin), distribution (mainly in small bronchi and bronchioles), or number (4.5 vs 4.1 cells per 10,000 epithelial cells, respectively) of endocrine cells.It seems unlikely that the substances secreted by these cells play any role in stimulating fibrosis in human lungs, but rather that they have a function in the inflammatory response to pulmonary injury.

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Endocrine cell proliferation in the rat lung following asbestos inhalation

Cited by 38 publications

References 12 publications

Increased pulmonary neuroendocrine cells with bombesin-like immunoreactivity in adult patients with eosinophilic granuloma.

Increased pulmonary neuroendocrine cells with bombesin-like immunoreactivity in adult patients with eosinophilic granuloma.

Hyperplasia of Alveolar Neuroendocrine Cells in Rat Lung Carcinogenesis by Silica with Selective Expression of Proadrenomedullin-Derived Peptides and Amidating Enzymes

Pulmonary endocrine cells in anthracosilicotic lungs

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