title: Expression of Carcinoembryonic Cell Adhesion Molecule 6 and Alveolar Epithelial Cell Markers in Lungs of Human Infants with Chronic Lung Disease.
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.
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (LWG, PW)
authors.forename: Linda W
authors.initials: LW
authors.lastname: Gonzales
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California (RG, LD)
authors.forename: Robert
authors.initials: R
authors.lastname: Gonzalez
authors.affiliation: Department of Pediatrics, University of California, San Francisco, San Francisco, California (AMB, PLB)
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Barrette
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania (LWG, PW)
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.affiliation: Cardiovascular Research Institute, University of California, San Francisco, San Francisco, California (RG, LD)
authors.forename: Leland
authors.initials: L
authors.lastname: Dobbs
authors.affiliation: Department of Pediatrics, University of California, San Francisco, San Francisco, California (AMB, PLB)
authors.forename: Philip L
authors.initials: PL
authors.lastname: Ballard
mesh_terms: D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D051402:Aquaporin 5 / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D002908:Chronic Disease; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D012131:Respiratory Insufficiency / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020545:Respiratory Mucosa / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors
chemical_list: C496036:AQP5 protein, human; D015703:Antigens, CD; D051402:Aquaporin 5; D015415:Biomarkers; C504117:CEACAM6 protein, human; D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D058851:GPI-Linked Proteins; C117055:HTI56 protein, human; D008565:Membrane Proteins; D018809:Proliferating Cell Nuclear Antigen; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; C504003:TTF1 protein, human; D014157:Transcription Factors
keywords: CEACAM6; alveolar epithelium; human lung development; human lung disease; lung injury; surfactant mutations; type I cells; type II cell hyperplasia; type II cells