Skip to main content
SpringerLink
Log in

Immunohistochemical expression of Napsin A in normal human fetal lungs at different gestational ages and in acquired and congenital pathological pulmonary conditions

  • Original Article
  • Published:
Virchows Archiv Aims and scope Submit manuscript

Abstract

Surfactant protein B (SP-B) is a key component of pulmonary surfactant. SP-B is processed to a mature, surface-active protein from a pro-peptide by two distinct cleavage events in its N-terminal and C-terminal regions. Napsin A, a protease expressed in type II pneumocytes, is responsible for the N-terminal cleavage event. Here, for the first time, we have evaluated the expression of Napsin A in normal fetal lungs at different gestational ages and in lungs from fetuses and neonates with congenital and acquired pathological pulmonary conditions. Lung samples were collected from fetal and neonatal autopsies at the Department of Medicine and Surgery’s Pathology Unit of Parma University (Italy). Immunohistochemical analysis was performed using a primary anti-Napsin A (clone IP64 clone) monoclonal antibody. A section of lung adenocarcinoma was used as an external positive control. Napsin A was expressed early in normal fetal lungs throughout the epithelium of the distal pseudoglandular tracts. In fetuses at 30 weeks of gestation and term newborns, Napsin A was already expressed only in isolated cells within the alveolar epithelium, similar to adult subjects. Furthermore, increased expression of Napsin A compared with a control group was observed in lung tissue from fetuses and a newborn with pathological conditions (inflammatory diseases and pulmonary hypoplasia). In conclusion, this study demonstrates that Napsin A is produced early in fetal life, and that its production is increased in many diseases, presumably in an effort to remedy functional pulmonary failure.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Lin S, Na CL, Akinbi HT, Apsley KS, Whitsett JA, Weaver TE (1999) Surfactant protein B (SP-B) -/- mice are rescued by restoration of SP-B expression in alveolar type II cells but not Clara cells. J Biol Chem 274:19168–19174. https://doi.org/10.1074/jbc.274.27.19168

    Article  CAS  PubMed  Google Scholar 

  2. Clark JC, Wert SE, Bachurski CJ, Stahlman MT, Stripp BR, Weaver TE, Whitsett JA (1995) Targeted disruption of the surfactant protein B gene disrupts surfactant homeostasis, causing respiratory failure in newborn mice. Proc Natl Acad Sci U S A 92:7794–7798. https://doi.org/10.1073/pnas.92.17.7794

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Nogee LM, Garnier G, Dietz HC, Singer L, Murphy AM, deMello DE, Colten HR (1994) A mutation in the surfactant protein B gene responsible for fatal neonatal respiratory disease in multiple kindreds. J Clin Invest 93:1860–1863. https://doi.org/10.1172/JCI117173

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Korimilli A, Gonzales LW, Guttentag SH (2000) Intracellular localization of processing events in human surfactant protein B biosynthesis. J Biol Chem 275:8672–8679. https://doi.org/10.1074/jbc.275.12.8672

    Article  CAS  PubMed  Google Scholar 

  5. Guttentag SH, Beers MF, Bieler BM, Ballard PL (1998) Surfactant protein B processing in human fetal lung. Am J Phys 275(3 Pt 1):L559–L566. https://doi.org/10.1152/ajplung.1998.275.3.L559

    Article  CAS  Google Scholar 

  6. Ueno T, Linder S, Na CL, Rice WR, Johansson J, Weaver TE (2004) Processing of pulmonary surfactant protein B by Napsin and cathepsin H. J Biol Chem 279:16178–16184. https://doi.org/10.1074/jbc.M312029200

    Article  CAS  PubMed  Google Scholar 

  7. Langley FA (1971) The perinatal postmortem examination. J Clin Pathol 24:159–169. https://doi.org/10.1136/jcp.24.2.159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Keeling JW (2007) The perinatal necroscopy. In: Keeling JW, Khong TY (eds) Fetal and Neonatal Pathology, 4th edn. springer-Verlag, London, pp 20–53

    Chapter  Google Scholar 

  9. Wigglesworth JS (1987) Pathology of the lung in the fetus and neonate, with particolar reference to problems of growth and maturation. Histopathology 11:671–678

    Article  CAS  Google Scholar 

  10. Kreiger PA (2011) Lung. In: Ernst LM, Ruchelli ED, Huff DS (eds) Color Atlas of Fetal and Neonatal Histology. Springer, New York, pp 21–35

    Chapter  Google Scholar 

  11. Matturri L, Biondo B, Mercurio P, Rossi L (2000) Severe hypoplasia of medullary arcuate nucleus: quantitative analysis in sudden infant death syndrome. Acta Neuropathol 99:371–375. https://doi.org/10.1007/s004010051138

    Article  CAS  PubMed  Google Scholar 

  12. Allanson JE, Pantzar JT, Macleod PM (1983) Possible new autosomal recessive syndrome with unusual renal histological changes. Am J Med Genet 6:57–60. https://doi.org/10.1002/ajmg.1320160110

    Article  Google Scholar 

  13. Dawe HR, Smith UM, Cullinane AR, Gerrelli D, Cox P, Badano JL, Blair-Reid S, Sriram N, Katsanis N, Attie-Bitach T, Afford SC, Copp AJ, Kelly DA, Gull K, Johnson CA (2007) The Meckel-Gruber syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation. Hum Mol Genet 16:173–186. https://doi.org/10.1093/hmg/ddl459

    Article  CAS  PubMed  Google Scholar 

  14. Hsia YE, Bratu M, Herbordt A (1971) Genetics of Meckel syndrome (dysencephalia-splanchnocystica). Pediatrics 48:237–247

    CAS  PubMed  Google Scholar 

  15. Majewski F, Stoss H, Goecke T, Kemperdick H (1983) Are bowing of long tubular bones and preaxial polydactyly signs of the Meckel syndrome? Hum Genet 65:125–133. https://doi.org/10.1007/BF00286648

    Article  CAS  PubMed  Google Scholar 

  16. Schauer-Vukasinovic V, Bur D, Kling D, Grüninger F, Giller T (1999) Human Napsin A: expression, immunochemical detection, and tissue localization. FEBS Lett 462:135–139. https://doi.org/10.1016/s0014-5793(99)01458-1

    Article  CAS  PubMed  Google Scholar 

  17. Ueno T, Linder S, Elmberger G (2003) Aspartic proteinase napsin is a useful marker for diagnosis of primary lung adenocarcinoma. Br J Cancer 88:1229–1233. https://doi.org/10.1038/sj.bjc.6600879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Shimoya K, Taniguchi T, Matsuzaki N, Moriyama A, Murata Y, Kitajima H, Fujimura M, Nakayama M (2000) Chorioamnionitis decreased incidence of respiratory distress syndrome by elevating fetal interleukin-6 serum concentration. Hum Reprod 15:2234–2240. https://doi.org/10.1093/humrep/15.10.2234

    Article  CAS  PubMed  Google Scholar 

  19. Auten RL, Watkins RH, Shapiro DL, Horowitz S (1990) Surfactant apoprotein A (SP-A) is synthesized in airway cells. Am J Respir Cell Mol Biol 3:491–496. https://doi.org/10.1165/ajrcmb/3.5.491

    Article  CAS  PubMed  Google Scholar 

  20. Kuan SF, Rust K, Crouch E (1992) Interactions of surfactant protein D with bacterial lipopolysaccharides. Surfactant protein D is an Escherichia coli-binding protein in bronchoalveolar lavage. J Clin Invest 90:97–106. https://doi.org/10.1172/JCI115861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Phelps DS, Floros J (1988) Localization of surfactant protein synthesis in human lung by in situ hybridization. Am Rev Respir Dis 137:939–942. https://doi.org/10.1164/ajrccm/137.4.939

    Article  CAS  PubMed  Google Scholar 

  22. Singh G, Singh J, Katyal SL, Brown WE, Kramps JA, Paradis IL, Dauber JH, Macpherson TA, Squeglia N (1988) Identification, cellular localization, isolation, and characterization of human Clara cell-specific 10 KD protein. J Histochem Cytochem 36:73–80. https://doi.org/10.1177/36.1.3275712

    Article  CAS  PubMed  Google Scholar 

  23. Cogo PE, Zimmermann LJ, Rosso F, Tormena F, Gamba P, Verlato G, Baritussio A, Carnielli VP (2002) Surfactant synthesis and kinetics in infants with congenital diaphragmatic hernia. Am J Respir Crit Care Med 166:154–158. https://doi.org/10.1164/rccm.2108028

    Article  PubMed  Google Scholar 

  24. Boucherat O, Benachi A, Chailley-Heu B, Franco-Montoya ML, Elie C, Martinovic J, Bourbon JR (2007) Surfactant maturation is not delayed in human fetuses with diaphragmatic hernia. PLoS Med 4:e237. https://doi.org/10.1371/journal.pmed.0040237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Davey MG, Biard JM, Robinson L, Tsai J, Schwarz U, Danzer E, Adzick NS, Flake AW, Hedrick HL (2005) Surfactant protein expression is increased in the ipsilateral but not contralateral lungs of fetal sheep with left-sided diaphragmatic hernia. Pediatr Pulmonol 39:359–367. https://doi.org/10.1002/ppul.20175

    Article  PubMed  Google Scholar 

  26. Pringle KC, Turner JW, Schofield JC, Soper RT (1984) Creation and repair of diaphragmatic hernia in the fetal lamb: lung development and morphology. J Pediatr Surg 19:131–140. https://doi.org/10.1016/S0022-3468(84)80432-7

  27. Hashimoto EG, Pringle KC, Soper RT, Brown CK (1985) The creation and repair of diaphragmatic hernia in fetal lambs: morphology of the type II alveolar cell. J Pediatr Surg 20:354–356. https://doi.org/10.1016/s0022-3468(85)80218-9

    Article  CAS  PubMed  Google Scholar 

  28. O'Reilly MA, Weaver TE, Pilot-Matias TJ, Sarin VK, Gazdar AF, Whitsett JA (1989) In vitro translation, post-translational processing and secretion of pulmonary surfactant protein B precursors. Biochim Biophys Acta 1011:140–148

    Article  CAS  Google Scholar 

  29. Uhal BD (1997) Cell cycle kinetics in the alveolar epithelium. Am J Phys 272(6 Pt 1):L1031–L1045. https://doi.org/10.1152/ajplung.1997.272.6.L1031

    Article  CAS  Google Scholar 

  30. Flecknoe SJ, Wallace MJ, Harding R, Hooper SB (2002) Determination of alveolar epithelial cell phenotypes in fetal sheep: evidence for the involvement of basal lung expansion. J Physiol 542(Pt 1):245–253. https://doi.org/10.1113/jphysiol.2001.014274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The authors wish to thank Mrs. Emilia Corradini for technical assistance.

Author information

Authors and Affiliations

  1. Department of Medicine and Surgery, Pathology Unit, University of Parma, Viale A. Gramsci, 14, 43126, Parma, Italy

    Giovanna Giordano, Nicoletta Campanini & Elena Varotti

Authors
  1. Giovanna Giordano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nicoletta Campanini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elena Varotti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giovanna Giordano.

Ethics declarations

This study was performed in compliance with the Helsinki Declaration and approved by the Ethics Committee of the Parma University Hospital (approval number 28700).

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Part of this work was presented as a poster during the 30th European Congress of Pathology, Bilbao, Spain, 08/09/2018–12/09/2018 and published as an abstract on Virchows Archiv 2018, 473 (Suppl 1), S309.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Quality in Pathology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Giordano, G., Campanini, N. & Varotti, E. Immunohistochemical expression of Napsin A in normal human fetal lungs at different gestational ages and in acquired and congenital pathological pulmonary conditions. Virchows Arch 477, 557–563 (2020). https://doi.org/10.1007/s00428-020-02809-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00428-020-02809-5

Keywords

Search

Navigation