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. 1993 May;91(5):1969–1973. doi: 10.1172/JCI116417

CD10/neutral endopeptidase 24.11 regulates fetal lung growth and maturation in utero by potentiating endogenous bombesin-like peptides.

K A King 1, J Hua 1, J S Torday 1, J M Drazen 1, S A Graham 1, M A Shipp 1, M E Sunday 1
PMCID: PMC288193  PMID: 8486767

Abstract

Bombesin-like peptides (BLPs) are mitogens for bronchial epithelial cells and small cell lung carcinomas, and increase fetal lung growth and maturation in utero and in organ cultures. BLPs are hydrolyzed by the enzyme CD10/neutral endopeptidase 24.11 (CD10/NEP) which is expressed in bronchial epithelium and functions to inhibit BLP-mediated growth of small cell lung carcinomas. To determine whether CD10/NEP regulates peptide-mediated lung development, we administered a specific CD10/NEP inhibitor, SCH32615, to fetal mice in utero from gestational days e15-17. Fetal lung tissues were evaluated on e18 for: (a) growth using [3H]thymidine incorporation into nuclear DNA; and (b) maturation using: [3H]-choline incorporation into surfactant phospholipids, electron microscopy for type II pneumocytes, and Northern blot analyses for surfactant apoproteins A, B, and C. Inhibition of CD10/NEP stimulated [3H]thymidine incorporation into DNA (70% above baseline, P < 0.005), [3H]choline incorporation into surfactant phospholipids (38% above baseline, P < 0.005), increased numbers of type II pneumocytes (36% above baseline, P = 0.07), and fivefold higher surfactant protein A transcripts (P < 0.05). CD10/NEP-mediated effects were completely blocked by the specific bombesin receptor antagonist, [D-Phe12, Leu14]bombesin. These observations suggest that CD10/NEP regulates fetal lung growth and maturation mediated by endogenous BLPs.

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Selected References

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  1. Aguayo S. M., King T. E., Jr, Waldron J. A., Jr, Sherritt K. M., Kane M. A., Miller Y. E. Increased pulmonary neuroendocrine cells with bombesin-like immunoreactivity in adult patients with eosinophilic granuloma. J Clin Invest. 1990 Sep;86(3):838–844. doi: 10.1172/JCI114782. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ballard P. L. Hormonal regulation of pulmonary surfactant. Endocr Rev. 1989 May;10(2):165–181. doi: 10.1210/edrv-10-2-165. [DOI] [PubMed] [Google Scholar]
  4. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  5. Bunnett N. W., Kobayashi R., Orloff M. S., Reeve J. R., Turner A. J., Walsh J. H. Catabolism of gastrin releasing peptide and substance P by gastric membrane-bound peptidases. Peptides. 1985 Mar-Apr;6(2):277–283. doi: 10.1016/0196-9781(85)90052-x. [DOI] [PubMed] [Google Scholar]
  6. Chen C. Y., Salles G., Seldin M. F., Kister A. E., Reinherz E. L., Shipp M. A. Murine common acute lymphoblastic leukemia antigen (CD10 neutral endopeptidase 24.11). Molecular characterization, chromosomal localization, and modeling of the active site. J Immunol. 1992 May 1;148(9):2817–2825. [PubMed] [Google Scholar]
  7. Chipkin R. E., Berger J. G., Billard W., Iorio L. C., Chapman R., Barnett A. Pharmacology of SCH 34826, an orally active enkephalinase inhibitor analgesic. J Pharmacol Exp Ther. 1988 Jun;245(3):829–838. [PubMed] [Google Scholar]
  8. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. D'Adamio L., Shipp M. A., Masteller E. L., Reinherz E. L. Organization of the gene encoding common acute lymphoblastic leukemia antigen (neutral endopeptidase 24.11): multiple miniexons and separate 5' untranslated regions. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7103–7107. doi: 10.1073/pnas.86.18.7103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Erdös E. G., Skidgel R. A. Neutral endopeptidase 24.11 (enkephalinase) and related regulators of peptide hormones. FASEB J. 1989 Feb;3(2):145–151. [PubMed] [Google Scholar]
  12. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  13. Heinz-Erian P., Coy D. H., Tamura M., Jones S. W., Gardner J. D., Jensen R. T. [D-Phe12]bombesin analogues: a new class of bombesin receptor antagonists. Am J Physiol. 1987 Mar;252(3 Pt 1):G439–G442. doi: 10.1152/ajpgi.1987.252.3.G439. [DOI] [PubMed] [Google Scholar]
  14. Jones D. T., Reed R. R. Molecular cloning of five GTP-binding protein cDNA species from rat olfactory neuroepithelium. J Biol Chem. 1987 Oct 15;262(29):14241–14249. [PubMed] [Google Scholar]
  15. Kenny A. J., O'Hare M. J., Gusterson B. A. Cell-surface peptidases as modulators of growth and differentiation. Lancet. 1989 Sep 30;2(8666):785–787. doi: 10.1016/s0140-6736(89)90841-6. [DOI] [PubMed] [Google Scholar]
  16. Letarte M., Vera S., Tran R., Addis J. B., Onizuka R. J., Quackenbush E. J., Jongeneel C. V., McInnes R. R. Common acute lymphocytic leukemia antigen is identical to neutral endopeptidase. J Exp Med. 1988 Oct 1;168(4):1247–1253. doi: 10.1084/jem.168.4.1247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Martins M. A., Shore S. A., Gerard N. P., Gerard C., Drazen J. M. Peptidase modulation of the pulmonary effects of tachykinins in tracheal superfused guinea pig lungs. J Clin Invest. 1990 Jan;85(1):170–176. doi: 10.1172/JCI114408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nadel J. A., Borson D. B. Modulation of neurogenic inflammation by neutral endopeptidase. Am Rev Respir Dis. 1991 Mar;143(3 Pt 2):S33–S36. doi: 10.1164/ajrccm/143.3_Pt_2.S33. [DOI] [PubMed] [Google Scholar]
  19. Nadel J. A. Decreased neutral endopeptidases: possible role in inflammatory diseases of airways. Lung. 1990;168 (Suppl):123–127. doi: 10.1007/BF02718124. [DOI] [PubMed] [Google Scholar]
  20. Phelps D. S., Floros J. Localization of pulmonary surfactant proteins using immunohistochemistry and tissue in situ hybridization. Exp Lung Res. 1991 Nov-Dec;17(6):985–995. doi: 10.3109/01902149109064330. [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. Salles G., Chen C. Y., Reinherz E. L., Shipp M. A. CD10/NEP is expressed on Thy-1low B220+ murine B-cell progenitors and functions to regulate stromal cell-dependent lymphopoiesis. Blood. 1992 Oct 15;80(8):2021–2029. [PubMed] [Google Scholar]
  23. Schellhase D. E., Shannon J. M. Effects of maternal dexamethasone on expression of SP-A, SP-B, and SP-C in the fetal rat lung. Am J Respir Cell Mol Biol. 1991 Apr;4(4):304–312. doi: 10.1165/ajrcmb/4.4.304. [DOI] [PubMed] [Google Scholar]
  24. Shipp M. A., Richardson N. E., Sayre P. H., Brown N. R., Masteller E. L., Clayton L. K., Ritz J., Reinherz E. L. Molecular cloning of the common acute lymphoblastic leukemia antigen (CALLA) identifies a type II integral membrane protein. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4819–4823. doi: 10.1073/pnas.85.13.4819. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Shipp M. A., Tarr G. E., Chen C. Y., Switzer S. N., Hersh L. B., Stein H., Sunday M. E., Reinherz E. L. CD10/neutral endopeptidase 24.11 hydrolyzes bombesin-like peptides and regulates the growth of small cell carcinomas of the lung. Proc Natl Acad Sci U S A. 1991 Dec 1;88(23):10662–10666. doi: 10.1073/pnas.88.23.10662. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shipp M. A., Vijayaraghavan J., Schmidt E. V., Masteller E. L., D'Adamio L., Hersh L. B., Reinherz E. L. Common acute lymphoblastic leukemia antigen (CALLA) is active neutral endopeptidase 24.11 ("enkephalinase"): direct evidence by cDNA transfection analysis. Proc Natl Acad Sci U S A. 1989 Jan;86(1):297–301. doi: 10.1073/pnas.86.1.297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. Stimler-Gerard N. P. Neutral endopeptidase-like enzyme controls the contractile activity of substance P in guinea pig lung. J Clin Invest. 1987 Jun;79(6):1819–1825. doi: 10.1172/JCI113023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sunday M. E., Hua J., Dai H. B., Nusrat A., Torday J. S. Bombesin increases fetal lung growth and maturation in utero and in organ culture. Am J Respir Cell Mol Biol. 1990 Sep;3(3):199–205. doi: 10.1165/ajrcmb/3.3.199. [DOI] [PubMed] [Google Scholar]
  30. Sunday M. E., Hua J., Torday J. S., Reyes B., Shipp M. A. CD10/neutral endopeptidase 24.11 in developing human fetal lung. Patterns of expression and modulation of peptide-mediated proliferation. J Clin Invest. 1992 Dec;90(6):2517–2525. doi: 10.1172/JCI116145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Sunday M. E., Willett C. G. Induction and spontaneous regression of intense pulmonary neuroendocrine cell differentiation in a model of preneoplastic lung injury. Cancer Res. 1992 May 1;52(9 Suppl):2677s–2686s. [PubMed] [Google Scholar]
  33. 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]

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