Expression of Carcinoembryonic Cell Adhesion Molecule 6 and Alveolar Epithelial Cell Markers in Lungs of Human Infants with Chronic Lung Disease

J Histochem Cytochem. 2015 Dec;63(12):908-21. doi: 10.1369/0022155415603768. Epub 2015 Sep 15.

Abstract

The membrane protein carcinoembryonic antigen cell adhesion molecule (CEACAM6) is expressed in the epithelium of various tissues, participating in innate immune defense, cell proliferation and differentiation, with overexpression in gastrointestinal tract, pancreatic and lung tumors. It is developmentally and hormonally regulated in fetal human lung, with an apparent increased production in preterm infants with respiratory failure. To further examine the expression and cell localization of CEACAM6, we performed immunohistochemical and biochemical studies in lung specimens from infants with and without chronic lung disease. CEACAM6 protein and mRNA were increased ~4-fold in lungs from infants with chronic lung disease as compared with controls. By immunostaining, CEACAM6 expression was markedly increased in the lung parenchyma of infants and children with a variety of chronic lung disorders, localizing to hyperplastic epithelial cells with a ~7-fold elevated proliferative rate by PCNA staining. Some of these cells also co-expressed membrane markers of both type I and type II cells, which is not observed in normal postnatal lung, suggesting they are transitional epithelial cells. We suggest that CEACAM6 is both a marker of lung epithelial progenitor cells and a contributor to the proliferative response after injury due to its anti-apoptotic and cell adhesive properties.

Keywords: CEACAM6; alveolar epithelium; human lung development; human lung disease; lung injury; surfactant mutations; type I cells; type II cell hyperplasia; type II cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, CD / genetics*
  • Antigens, CD / metabolism
  • Aquaporin 5 / genetics
  • Aquaporin 5 / metabolism
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cell Adhesion Molecules / genetics*
  • Cell Adhesion Molecules / metabolism
  • Chronic Disease
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gene Expression
  • Humans
  • Infant
  • Infant, Newborn
  • Lung / metabolism
  • Lung / pathology
  • Lung Diseases / genetics*
  • Lung Diseases / metabolism
  • Lung Diseases / pathology
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • Pulmonary Surfactants / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Respiratory Insufficiency / genetics*
  • Respiratory Insufficiency / metabolism
  • Respiratory Insufficiency / pathology
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / pathology
  • Stem Cells / metabolism
  • Stem Cells / pathology
  • Transcription Factors

Substances

  • AQP5 protein, human
  • Antigens, CD
  • Aquaporin 5
  • Biomarkers
  • CEACAM6 protein, human
  • Cell Adhesion Molecules
  • DNA-Binding Proteins
  • GPI-Linked Proteins
  • HTI56 protein, human
  • Membrane Proteins
  • Proliferating Cell Nuclear Antigen
  • Pulmonary Surfactants
  • RNA, Messenger
  • TTF1 protein, human
  • Transcription Factors