SpringerLink
Log in

Amniotic Sac Infection Syndrome Features Fetal Lung Neuroendocrine Cell Hyperfunction

  • Published:
Pediatric and Developmental Pathology

Abstract

Neuroendocrine cells (NEC) are abundant in fetal and neonatal lungs, but reduced in infants with hyaline membrane disease. Perinatal neuroendocrine cell hyperplasia (NCH) has been reported in the hypoplastic lung in diaphragmatic hernia, bronchopulmonary dysplasia, and Wilson-Mikity syndrome. Since we are unaware of any reports on NCH in fetal inflammatory conditions, this report addresses the NEC in fetuses with congenital pneumonia. Twenty-one fetuses/neonates with congenital pneumonia, autopsied between 1995 and 2001, were compared to 21 fetuses without a congenital infection matched for gestational age. Lung sections were immunostained for chromogranin, bombesin, calcitonin, and synaptophysin. Proportions of immunopositive cells lining 20 consecutive bronchioles calculated from digital images were significantly higher in the study than the control group for chromogranin (1.8 vs. 0.8%, P = 2.4E-06), calcitonin (1.2 vs. 0.7%, P = 0.005), and bombesin (1.1 vs. 0.7%, P = 0.005). There was no difference in synaptophysin (11.7% vs. 12.6%, P = 0.07). The absence of significant differences in the synaptophysin ratio excludes simple NCH in the study group. The synchronous increase in three neurohormones is indicative of NEC hyperfunction, due to either altered enzymatic inactivation by neutral endopeptidase, known to be reduced in adult lung inflammation, or by an increase in expression of the neurohormone genes. These data indicate that NEC hyperfunction may be responsible for the deranged fetal/neonatal lung function and circulatory adaptation, and contribute to the lethality of the amniotic sac infection syndrome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. F Feyrter (1946) ArticleTitleÜber die these von den peripheren endokrinen Drusen. Wien Z Inn Med Grenz 10 9–36

    Google Scholar 

  2. F Fröhlich (1949) ArticleTitleDie Helle Zeller der Bronchialschleimhaut und ihre Beziehungen zum Problem der Chemoreceptoren. Frankfurter Z Pathol 60 517–559

    Google Scholar 

  3. R Glorieux (1963) ArticleTitleLes cellules argentaffines du poumon et leurs connexions avec le system nerveux. Arch Biol 74 377–390 Occurrence Handle1:STN:280:CCuD2s%2Fmt1w%3D

    CAS  Google Scholar 

  4. MI Shul’ga (1964) ArticleTitleIslet receptors of the lungs. Arkh Anat Gistol Embriol 47 87–89 Occurrence Handle1:STN:280:CCqD2crpvVc%3D Occurrence Handle14241553

    CAS  PubMed  Google Scholar 

  5. JM Lauweryns JC Peuskens (1972) ArticleTitleNeuroepithelial bodies (neuroreceptor or secretory organs?) in human infant bronchial epithelium. Anat Rec 172 471–482 Occurrence Handle1:STN:280:CS2C3szgvFw%3D Occurrence Handle4110997

    CAS  PubMed  Google Scholar 

  6. VE Gould I Lee WH Warren (1998) ArticleTitleImmunohistochemical evaluation of neuroendocrine cells and neoplasms of the lung. Pathol Res Pract 183 200–213

    Google Scholar 

  7. D Adriaensen D Scheurmann (1993) ArticleTitleNeuroendocrine cells and nerves of the lung. Anat Rec 236 70–85 Occurrence Handle1:STN:280:ByyB1c3lvV0%3D Occurrence Handle7685156

    CAS  PubMed  Google Scholar 

  8. SP Sorokin RF Hayt Jr (1993) ArticleTitleWorkshop on pulmonary neuroendocrine cells in health and disease. Anat Rec 236 1–256 Occurrence Handle8099473

    PubMed  Google Scholar 

  9. H Watanabe (1988) ArticleTitlePathological studies on neuroendocrine cells in human embryonic and fetal lung. Light microscopical, immunohistochemical and electron microscopical approaches. Acta Pathol Jpn 38 59–74 Occurrence Handle1:STN:280:BieB3cnotVA%3D Occurrence Handle2834913

    CAS  PubMed  Google Scholar 

  10. P Xu S Hashimoto H Miyazaki K Asabe S Shiraishi K Sueishi (1998) ArticleTitleMorphometric analysis of the immunohistochemical expression of Clara cell 10-kDa protein and surfactant apoproteins A and B in the develo** bronchi and bronchioles of human fetuses and neonates. Virchows Arch 432 17–25 Occurrence Handle10.1007/s004280050129 Occurrence Handle1:CAS:528:DyaK1cXjtlSnuw%3D%3D Occurrence Handle9463583

    Article  CAS  PubMed  Google Scholar 

  11. Y Tsutsumi RY Osamura K Watanabe N Yanaihara (1983) ArticleTitleImmunohistochemical studies on gastrin-releasing peptide- and adrenocorticotropic hormone-containing cells in the human lung. Lab Invest 48 623–632 Occurrence Handle1:STN:280:BiyC1M%2FlsFc%3D Occurrence Handle6188883

    CAS  PubMed  Google Scholar 

  12. DG Perrin TJ McDonald E Cutz (1991) ArticleTitleHyperplasia of bombesin-immunoreactive pulmonary neuroendocrine cells and neuroepithelial bodies in infant death syndrome. Pediatr Pathol 11 431–447 Occurrence Handle1:STN:280:By6A38nntFA%3D Occurrence Handle1714077

    CAS  PubMed  Google Scholar 

  13. JR Gosney (1993) ArticleTitleNeuroendocrine cell populations in postnatal human lungs: minimal variation from childhood to old age. Anat Rec 236 177–180 Occurrence Handle1:STN:280:ByyB1c3lslA%3D Occurrence Handle8507004

    CAS  PubMed  Google Scholar 

  14. W Taylor (1977) ArticleTitlePulmonary argyrophil cells at high altitude. J Pathol 122 137–144 Occurrence Handle1:STN:280:CSiB38bosVw%3D Occurrence Handle886399

    CAS  PubMed  Google Scholar 

  15. RP DiAugustine KS Sonstegard (1984) ArticleTitleNeuroendocrine-like (small granules) epithelial cells of the lung. Environ Health Perspect 55 271–295 Occurrence Handle1:STN:280:BiuB3srpsVE%3D Occurrence Handle6376101

    CAS  PubMed  Google Scholar 

  16. D Adriaensen DW Scheuermann M Gajda I Brouns JP Timmermans (2001) ArticleTitleFunctional implications of extensive new data on the innervation of pulmonary neuroepithelial bodies. It J Anat Embryol 106 IssueIDSuppl 2 395–403 Occurrence Handle1:STN:280:DC%2BD3MnotlClsQ%3D%3D

    CAS  Google Scholar 

  17. JR Gosney MCJ Sissons RO Allibone AF Blakey (1989) ArticleTitlePulmonary endocrine cells in chronic bronchitis and emphysema. J Pathol 157 127–133 Occurrence Handle1:STN:280:BiaC2Mjit1Q%3D Occurrence Handle2921673

    CAS  PubMed  Google Scholar 

  18. HK Plummer III BJ Sheppard HM Schuller (2000) ArticleTitleInteraction of tobacco-specific toxicants with nicotinic cholinergic regulation of fetal pulmonary neuroendocrine cells: implications for pediatric lung disease. Exp Lung Res 26 121–135 Occurrence Handle10.1080/019021400269916 Occurrence Handle10742926

    Article  PubMed  Google Scholar 

  19. M Sunday J Hua B Reyes H Masui J Torday (1993) ArticleTitleAnti-bombesin antibodies modulate fetal mouse lung growth and maturation in utero and in organ cultures. Anat Rec 236 25–32 Occurrence Handle1:CAS:528:DyaK3sXlsFantbY%3D Occurrence Handle8507013

    CAS  PubMed  Google Scholar 

  20. KA King J Hua JS Torday JM Drazen SA Graham MA Shipp (1993) ArticleTitleCD10/neutral endopeptidase 24.11 regulates fetal lung growth and maturation in utero by potentiating endogenous bombesin-like peptides. J Clin Invest 91 1969–1973 Occurrence Handle1:CAS:528:DyaK3sXktVWksbg%3D Occurrence Handle8486767

    CAS  PubMed  Google Scholar 

  21. RL Emanuel JS Torday Q Mu N Asokananthan KA Sikorski ME Sunday (1999) ArticleTitleBombesin-like peptides and receptors in normal fetal baboon lung: roles in lung growth and maturation. Am J Physiol 277 L1003–L1017 Occurrence Handle1:CAS:528:DyaK1MXns1Oksbw%3D Occurrence Handle10564187

    CAS  PubMed  Google Scholar 

  22. AJ Cohen TE King Jr LB Gilman C Magill-Solc YE Miller (1998) ArticleTitleHigh expression of neutral endopeptidase in idiopathic diffuse hyperplasia of pulmonary neuroendocrine cells. Am J Respir Crit Care Med 158 1593–1599 Occurrence Handle1:STN:280:DyaK1M%2FjsVOnug%3D%3D Occurrence Handle9817713

    CAS  PubMed  Google Scholar 

  23. ME Sunday J Hua HB Dai A Nusrat JS Torday (1990) ArticleTitleBombesin increases fetal lung growth and maturation in utero and in organ culture. Am J Respir Cell Mol Biol 3 199–205 Occurrence Handle1:CAS:528:DyaK3MXmt1CitL4%3D Occurrence Handle2390263

    CAS  PubMed  Google Scholar 

  24. P Van den Steen EK Verbeken A Van Lommel JM Lauweryns (1997) ArticleTitleImmunoreactivity for the alpha-subunit of the pituitary glycoprotein hormones in pulmonary neuroendocrine cells of develo** human lung and various perinatal diseases. Regul Pept 70 37–48 Occurrence Handle10.1016/S0167-0115(97)00016-5 Occurrence Handle1:CAS:528:DyaK2sXks1Kmsr0%3D Occurrence Handle9250580

    Article  CAS  PubMed  Google Scholar 

  25. DE Johnson WR Anderson BA Burke (1993) ArticleTitlePulmonary neuroendocrine cells in pediatric lung disease: alterations in airway structure in infants with bronchopulmonary dysplasia. Anat Rec 236 115–119 Occurrence Handle1:STN:280:ByyB1c3ls1E%3D Occurrence Handle8506996

    CAS  PubMed  Google Scholar 

  26. VA Memoli I Linnoila WH Warren J Rios-Dalenz VE Gould (1983) ArticleTitleHyperplasia of neuroendocrine cells and neuroepithelial bodies (Abstract). Lab Invest 48 57

    Google Scholar 

  27. DE Johnson JD Wobken BG Landrum (1988) ArticleTitleChanges in bombesin, calcitonin, and serotonin immunoreactive pulmonary neuroendocrine cells in cystic fibrosis and after prolonged mechanical ventilation. Am Rev Respir Dis 137 123–131 Occurrence Handle1:STN:280:BieC3cvoslY%3D Occurrence Handle3337452

    CAS  PubMed  Google Scholar 

  28. J Gosney D Health P Smith P Harris M Yacoub (1989) ArticleTitlePulmonary endocrine cells in pulmonary arterial disease. Arch Pathol Lab Med 113 337–341 Occurrence Handle1:STN:280:BiaB3cnksFY%3D Occurrence Handle2705865

    CAS  PubMed  Google Scholar 

  29. M Sunday L Kaplan E Motoyama W Chin E Spindel (1988) ArticleTitleBiology of disease: gastrin-related peptide (mammalian bombesin) gene expression in health and disease. Lab Invest 59 5–24 Occurrence Handle1:CAS:528:DyaL1cXltVCrtLo%3D Occurrence Handle2839735

    CAS  PubMed  Google Scholar 

  30. S Aguayo (1993) ArticleTitlePulmonary neuroendocrine cells in tobacco-related lung disorders. Anat Rec 236 122–127 Occurrence Handle1:STN:280:ByyB1c3ls1I%3D Occurrence Handle8506997

    CAS  PubMed  Google Scholar 

  31. SM Aguano (1993) ArticleTitlePulmonary neuroendocrine cells in tobacco-related lung disorders. Anat Rec 236 122–127 Occurrence Handle1:STN:280:ByyB1c3ls1I%3D Occurrence Handle8506997

    CAS  PubMed  Google Scholar 

  32. DS Bonikos R Archibald KG Bensch (1976) ArticleTitleOn the origin of the so-called tumorlets of the lung. Hum Pathol 37 1977–1998 Occurrence Handle1:STN:280:CSmC283ps10%3D

    CAS  Google Scholar 

  33. E Cutz W Chan D Perrin (1988) ArticleTitlePulmonary neuroendocrine cells in SIDS. An immunohistochemical and quantitative study. Ann NY Acad Sci 533 461–463

    Google Scholar 

  34. JE Gillan E Cutz (1993) ArticleTitleAbnormal pulmonary bombesin immunoreactive cells in Wilson-Mikity syndrome (pulmonary dysmaturity) and bronchopulmonary dysplasia. Pediatr Pathol 13 165–180 Occurrence Handle1:STN:280:ByyB3MbitVc%3D Occurrence Handle8464778

    CAS  PubMed  Google Scholar 

  35. KCL Carlsen KH Carlsen (2001) ArticleTitleEffects of maternal and early tobacco exposure on the development of asthma and airway hyperreactivity. Curr Opin Allergy Clin Immunol 1 139–143 Occurrence Handle10.1097/01.all.0000010998.15560.b6 Occurrence Handle11964681

    Article  PubMed  Google Scholar 

  36. DE Johnson TJ Kulik JE Lock RP Elde TR Thompson (1985) ArticleTitleBombesin-, calcitonin-, and serotonin-immunoreactive pulmonary neuroendocrine cells in acute and chronic neonatal lung disease. Pediatr Pulmonol 1 IssueIDSuppl 3 S13–S20 Occurrence Handle1:STN:280:BimD28nosFM%3D Occurrence Handle4069801

    CAS  PubMed  Google Scholar 

  37. JP Joad C Ji KS Kott JM Bric KE Pinkerton (1995) ArticleTitleIn utero and postnatal effects of sidestream cigarette smoke exposure on lung function, hyperresponsiveness, and neuroendocrine cells in rats. Toxicol Appl Pharmacol 132 63–71 Occurrence Handle10.1006/taap.1995.1087 Occurrence Handle1:CAS:528:DyaK2MXlsF2it7k%3D Occurrence Handle7747286

    Article  CAS  PubMed  Google Scholar 

  38. T Yamataka P Puri (1996) ArticleTitleIncreased intracellular levels of calcitonin gene-related peptide-like immunoreactivity in pulmonary endocrine cells in an experimental model of congenital diaphragmatic hernia. Pediatr Surg Int 11 448–452 Occurrence Handle10.1007/BF00180080

    Article  Google Scholar 

  39. H IJsselstijn DG Perrin JC de Jongste E Cutz D Tibboel (1995) ArticleTitlePulmonary neuroendocrine cells in neonatal rats with congenital diaphragmatic hernia. J Pediatr Surg 30 413–415 Occurrence Handle10.1016/0022-3468(95)90044-6 Occurrence Handle1:STN:280:ByqB1c%2FitVI%3D Occurrence Handle7760232

    Article  CAS  PubMed  Google Scholar 

  40. RL Emanuel JS Torday Q Mu N Asokananthan KA Sikorski ME Sunday (1999) ArticleTitleBombesin-like peptides and receptors in normal fetal baboon lung: roles in lung growth and maturation. Am J Physiol 277 IssueID5 Pt 1 L1003–1017 Occurrence Handle1:CAS:528:DyaK1MXns1Oksbw%3D Occurrence Handle10564187

    CAS  PubMed  Google Scholar 

  41. JR Gosney (1983) ArticleTitlePulmonary neuroendocrine cells in species at high altitude. Anat Rec 236 105–107

    Google Scholar 

  42. JW Keeling (1993) Fetal and neonatal pathology, 2nd ed. Springer-Verlag London

    Google Scholar 

  43. RL Naye SM Ross (1982) ArticleTitleAmniotic fluid infection syndrome. Clin Obstet Gynecol 9 593–606

    Google Scholar 

  44. YW Wu JM Colford (2000) ArticleTitleChorioamnionitis as a risk factor for cerebral palsy. JAMA 284 1417–1424 Occurrence Handle10.1001/jama.284.11.1417 Occurrence Handle1:STN:280:DC%2BD3cvktlKrtA%3D%3D Occurrence Handle10989405

    Article  CAS  PubMed  Google Scholar 

  45. S Remington JO Klein (1995) Infectious diseases of the fetus and newborn. W.B. Saunders Philadelphia

    Google Scholar 

  46. SJ Gould PG Isaacson (1993) ArticleTitleBronchus-associated lymphoid tissue (BALT) in human fetal and infant lung. J Pathol 169 229–234 Occurrence Handle1:STN:280:ByyC1cjns1U%3D Occurrence Handle8445488

    CAS  PubMed  Google Scholar 

  47. I Lee VE Gould R Moll B Wiedenmann WW Franke (1987) ArticleTitleSynaptophysin expressed in the bronchopulmonary tract: neuroendocrine cells, neuroepithelial bodies, and neuroendocrine neoplasms. Differentiation 34 115–125 Occurrence Handle1:STN:280:BiiA3critlc%3D Occurrence Handle2442053

    CAS  PubMed  Google Scholar 

  48. SM Jensen AF Gazdar F Cuttitta EK Russell RI Linnoila (1990) ArticleTitleA comparison of synaptophysin, chromogranin, and L-dopa decarboxylase as markers for neuroendocrine differentiation in lung cancer cell lines. Cancer Res 50 6068–6074 Occurrence Handle1:CAS:528:DyaK3cXmtV2it7c%3D Occurrence Handle2168288

    CAS  PubMed  Google Scholar 

  49. J Wharton JM Polak GA Cole PJ Marangos AGE Pearse (1981) ArticleTitleNeuron-specific enolase as an immunocytochemical marker for the diffuse neuroendocrine system in human fetal lung. J Histochem Cytochem 29 1359–1364 Occurrence Handle1:CAS:528:DyaL38XjtV2qsA%3D%3D Occurrence Handle7033363

    CAS  PubMed  Google Scholar 

  50. CE Wood D Barkoe A The et al. (1998) ArticleTitleFetal pulmonary immunoreactive adrenocorticotropin: molecular weight and cellular localization. Regul Pept 73 191–196 Occurrence Handle10.1016/S0167-0115(98)00004-4 Occurrence Handle1:CAS:528:DyaK1cXhsFensLo%3D Occurrence Handle9556082

    Article  CAS  PubMed  Google Scholar 

  51. VH Van der Velden AR Hulsmann (1999) ArticleTitlePeptidases: structure, function and modulation of peptide-mediated effects in the human lung. Clin Exp Allergy 29 445–456 Occurrence Handle10.1046/j.1365-2222.1999.00462.x Occurrence Handle1:CAS:528:DyaK1M**slejsr8%3D Occurrence Handle10202358

    Article  CAS  PubMed  Google Scholar 

  52. MT Stahlman M Jones ME Gray AG Kasselberg WK Vaughn (1987) ArticleTitleOntogeny of neuroendocrine cells in human fetal lung. III. An electron microscopic immunohistochemical study. Lab Invest 56 629–641 Occurrence Handle1:STN:280:BiiB2MrosVM%3D Occurrence Handle3599909

    CAS  PubMed  Google Scholar 

  53. J Stanek (1996) ArticleTitleDistribution of membrane metalloendopeptidase (CD10), microsomal endopeptidase (CD13), and aminopeptidase A (CD26) in third trimester placentas from uncomplicated pregnancies (Abstract). Mod Pathol 9 51A

    Google Scholar 

  54. H Kohrogi JA Nadel B Malfroy et al. (1989) ArticleTitleRecombinant human enkephalinase (neutral endopeptidases) prevents cough induced by tachykinins in awake guinea pigs. J Clin Invest 84 781–786 Occurrence Handle1:CAS:528:DyaK3cXkvVc%3D Occurrence Handle2474575

    CAS  PubMed  Google Scholar 

  55. Nadel, JA (1990) Decreased neutral endopeptidase: possible role in inflammatory diseases of airways. Lung (Suppl):123–127.

  56. CM Lilly L Kobzik AE Hall JM Drazen (1994) ArticleTitleEffects of chronic inflammation on the activity and enzymatic inactivation of neuropeptides in guinea pig lungs. J Clin Invest 93 2667–2674 Occurrence Handle1:CAS:528:DyaK2cXlsFCmt7g%3D Occurrence Handle7515394

    CAS  PubMed  Google Scholar 

  57. WL Castleman DL Dungworth LW Schwartz WS Tyler (1980) ArticleTitleAcute respiratory bronchiolitis: an ultrastructural and autoradiographic study of epithelial cell injury and renewal in rhesus monkeys exposed to ozone. Am J Pathol 98 811–840 Occurrence Handle1:STN:280:Bi%2BC2M7gs1E%3D Occurrence Handle6767409

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study was presented at the ASCP & CAP Annual Meeting in Washington, DC, October 12–15, 2002.

Author information

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, 231 Albert Sabin Way, P.O. Box 670529, Cincinnati, OH 45267-0529, USA

    Aly G. Saad, Sue Heffelfinger & Jerzy Stanek

Authors
  1. Aly G. Saad
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sue Heffelfinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jerzy Stanek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jerzy Stanek.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Saad, A., Heffelfinger, S. & Stanek, J. Amniotic Sac Infection Syndrome Features Fetal Lung Neuroendocrine Cell Hyperfunction . Pediatr. Dev. Pathol. 6, 484–494 (2003). https://doi.org/10.1007/s10024-003-1115-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10024-003-1115-0

Keywords

Search

Navigation