Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Sep;86(3):838–844. doi: 10.1172/JCI114782

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

S M Aguayo 1, T E King Jr 1, J A Waldron Jr 1, K M Sherritt 1, M A Kane 1, Y E Miller 1
PMCID: PMC296800  PMID: 2394833

Abstract

Cigarette 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 1 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.

Full text

PDF
838

Images in this article

841Image
on p.841

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AULD D. Pathology of eosinophilic granuloma of the lung. AMA Arch Pathol. 1957 Feb;63(2):113–131. [PubMed] [Google Scholar]
  2. Aguayo S. M., Kane M. A., King T. E., Jr, Schwarz M. I., Grauer L., Miller Y. E. Increased levels of bombesin-like peptides in the lower respiratory tract of asymptomatic cigarette smokers. J Clin Invest. 1989 Oct;84(4):1105–1113. doi: 10.1172/JCI114273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Basset F., Soler P., Hance A. J. The Langerhans' cell in human pathology. Ann N Y Acad Sci. 1986;465:324–339. doi: 10.1111/j.1749-6632.1986.tb18508.x. [DOI] [PubMed] [Google Scholar]
  4. Bettger W. J., Boyce S. T., Walthall B. J., Ham R. G. Rapid clonal growth and serial passage of human diploid fibroblasts in a lipid-enriched synthetic medium supplemented with epidermal growth factor, insulin, and dexamethasone. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5588–5592. doi: 10.1073/pnas.78.9.5588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. CUNNINGHAM G. J., NASSAU E., WALTER J. B. The frequency of tumour-like formations in bronchiectatic lungs. Thorax. 1958 Mar;13(1):64–68. doi: 10.1136/thx.13.1.64. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Crystal R. G., Bitterman P. B., Rennard S. I., Hance A. J., Keogh B. A. Interstitial lung diseases of unknown cause. Disorders characterized by chronic inflammation of the lower respiratory tract (first of two parts). N Engl J Med. 1984 Jan 19;310(3):154–166. doi: 10.1056/NEJM198401193100304. [DOI] [PubMed] [Google Scholar]
  7. Cuttitta F., Carney D. N., Mulshine J., Moody T. W., Fedorko J., Fischler A., Minna J. D. Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer. 1985 Aug 29-Sep 4Nature. 316(6031):823–826. doi: 10.1038/316823a0. [DOI] [PubMed] [Google Scholar]
  8. Day R., Lemaire I., Masse S., Lemaire S. Pulmonary bombesin in experimentally induced asbestosis in rats. Exp Lung Res. 1985;8(1):1–13. doi: 10.3109/01902148509069676. [DOI] [PubMed] [Google Scholar]
  9. Erspamer V., Erpamer G. F., Inselvini M. Some pharmacological actions of alytesin and bombesin. J Pharm Pharmacol. 1970 Nov;22(11):875–876. doi: 10.1111/j.2042-7158.1970.tb08465.x. [DOI] [PubMed] [Google Scholar]
  10. Friedman P. J., Liebow A. A., Sokoloff J. Eosinophilic granuloma of lung. Clinical aspects of primary histiocytosis in the adult. Medicine (Baltimore) 1981 Nov;60(6):385–396. [PubMed] [Google Scholar]
  11. Gosney J. R., Sissons M. C., Allibone R. O., Blakey A. F. Pulmonary endocrine cells in chronic bronchitis and emphysema. J Pathol. 1989 Feb;157(2):127–133. doi: 10.1002/path.1711570207. [DOI] [PubMed] [Google Scholar]
  12. Gosney J. R., Sissons M. C., Allibone R. O. Neuroendocrine cell populations in normal human lungs: a quantitative study. Thorax. 1988 Nov;43(11):878–882. doi: 10.1136/thx.43.11.878. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gould V. E., Linnoila R. I., Memoli V. A., Warren W. H. Neuroendocrine components of the bronchopulmonary tract: hyperplasias, dysplasias, and neoplasms. Lab Invest. 1983 Nov;49(5):519–537. [PubMed] [Google Scholar]
  14. Hance A. J., Basset F., Saumon G., Danel C., Valeyre D., Battesti J. P., Chrétien J., Georges R. Smoking and interstitial lung disease. The effect of cigarette smoking on the incidence of pulmonary histiocytosis X and sarcoidosis. Ann N Y Acad Sci. 1986;465:643–656. doi: 10.1111/j.1749-6632.1986.tb18541.x. [DOI] [PubMed] [Google Scholar]
  15. Johnson D. E., Lock J. E., Elde R. P., Thompson T. R. Pulmonary neuroendocrine cells in hyaline membrane disease and bronchopulmonary dysplasia. Pediatr Res. 1982 Jun;16(6):446–454. doi: 10.1203/00006450-198206000-00009. [DOI] [PubMed] [Google Scholar]
  16. Johnson D. E., Wobken J. D., Landrum B. G. Changes in bombesin, calcitonin, and serotonin immunoreactive pulmonary neuroendocrine cells in cystic fibrosis and after prolonged mechanical ventilation. Am Rev Respir Dis. 1988 Jan;137(1):123–131. doi: 10.1164/ajrccm/137.1.123. [DOI] [PubMed] [Google Scholar]
  17. Johnson N. F., Wagner J. C., Wills H. A. Endocrine cell proliferation in the rat lung following asbestos inhalation. Lung. 1980;158(4):221–228. doi: 10.1007/BF02713725. [DOI] [PubMed] [Google Scholar]
  18. Kleinerman J., Marchevsky A. M., Thornton J. Quantitative studies of APUD cells in airways of rats. The effects of diethylnitrosamine and NO2. Am Rev Respir Dis. 1981 Oct;124(4):458–462. doi: 10.1164/arrd.1981.124.4.458. [DOI] [PubMed] [Google Scholar]
  19. Lauweryns J. M., Cokelaere M., Deleersynder M., Liebens M. Intrapulmonary neuro-epithelial bodies in newborn rabbits. Influence of hypoxia, hyperoxia, hypercapnia, nicotine, reserpine, L-DOPA and 5-HTP. Cell Tissue Res. 1977 Sep 5;182(4):425–440. doi: 10.1007/BF00219827. [DOI] [PubMed] [Google Scholar]
  20. Reynolds H. Y. Bronchoalveolar lavage. Am Rev Respir Dis. 1987 Jan;135(1):250–263. doi: 10.1164/arrd.1987.135.1.250. [DOI] [PubMed] [Google Scholar]
  21. Rozengurt E., Sinnett-Smith J. Bombesin stimulation of DNA synthesis and cell division in cultures of Swiss 3T3 cells. Proc Natl Acad Sci U S A. 1983 May;80(10):2936–2940. doi: 10.1073/pnas.80.10.2936. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ruff M., Schiffmann E., Terranova V., Pert C. B. Neuropeptides are chemoattractants for human tumor cells and monocytes: a possible mechanism for metastasis. Clin Immunol Immunopathol. 1985 Dec;37(3):387–396. doi: 10.1016/0090-1229(85)90108-4. [DOI] [PubMed] [Google Scholar]
  23. Soler P., Moreau A., Basset F., Hance A. J. Cigarette smoking-induced changes in the number and differentiated state of pulmonary dendritic cells/Langerhans cells. Am Rev Respir Dis. 1989 May;139(5):1112–1117. doi: 10.1164/ajrccm/139.5.1112. [DOI] [PubMed] [Google Scholar]
  24. Spindel E. R., Krane I. M. Molecular biology of bombesin-like peptides. Comparison of cDNAs encoding human gastrin-releasing peptide, human neuromedin B, and amphibian ranatensin. Ann N Y Acad Sci. 1988;547:10–20. doi: 10.1111/j.1749-6632.1988.tb23871.x. [DOI] [PubMed] [Google Scholar]
  25. Spindel E. R., Sunday M. E., Hofler H., Wolfe H. J., Habener J. F., Chin W. W. Transient elevation of messenger RNA encoding gastrin-releasing peptide, a putative pulmonary growth factor in human fetal lung. J Clin Invest. 1987 Oct;80(4):1172–1179. doi: 10.1172/JCI113176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sunday M. E., Kaplan L. M., Motoyama E., Chin W. W., Spindel E. R. Gastrin-releasing peptide (mammalian bombesin) gene expression in health and disease. Lab Invest. 1988 Jul;59(1):5–24. [PubMed] [Google Scholar]
  27. Tabassian A. R., Nylen E. S., Linnoila R. I., Snider R. H., Cassidy M. M., Becker K. L. Stimulation of hamster pulmonary neuroendocrine cells and associated peptides by repeated exposure to cigarette smoke. Am Rev Respir Dis. 1989 Aug;140(2):436–440. doi: 10.1164/ajrccm/140.2.436. [DOI] [PubMed] [Google Scholar]
  28. Taylor W. Pulmonary argyrophil cells at high altitude. J Pathol. 1977 Jul;122(3):137–144. doi: 10.1002/path.1711220304. [DOI] [PubMed] [Google Scholar]
  29. Wang N. S., Chen M. F., Schraufnagel D. E., Yao Y. T. The cumulative scanning electron microscopic changes in baby mouse lungs following prenatal and postnatal exposures to nicotine. J Pathol. 1984 Oct;144(2):89–100. doi: 10.1002/path.1711440204. [DOI] [PubMed] [Google Scholar]
  30. Watters L. C., Schwarz M. I., Cherniack R. M., Waldron J. A., Dunn T. L., Stanford R. E., King T. E. Idiopathic pulmonary fibrosis. Pretreatment bronchoalveolar lavage cellular constituents and their relationships with lung histopathology and clinical response to therapy. Am Rev Respir Dis. 1987 Mar;135(3):696–704. doi: 10.1164/arrd.1987.135.3.696. [DOI] [PubMed] [Google Scholar]
  31. Wharton J., Polak J. M., Bloom S. R., Ghatei M. A., Solcia E., Brown M. R., Pearse A. G. Bombesin-like immunoreactivity in the lung. Nature. 1978 Jun 29;273(5665):769–770. doi: 10.1038/273769a0. [DOI] [PubMed] [Google Scholar]
  32. Willey J. C., Lechner J. F., Harris C. C. Bombesin and the C-terminal tetradecapeptide of gastrin-releasing peptide are growth factors for normal human bronchial epithelial cells. Exp Cell Res. 1984 Jul;153(1):245–248. doi: 10.1016/0014-4827(84)90466-x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES