title: Basal cells contribute to innate immunity of the airway epithelium through production of the antimicrobial protein RNase 7.
abstract: Basal cells play a critical role in the response of the airway epithelium to injury and are recently recognized to also contribute to epithelial immunity. Antimicrobial proteins and peptides are essential effector molecules in this airway epithelial innate immunity. However, little is known about the specific role of basal cells in antimicrobial protein and peptide production and about the regulation of the ubiquitous antimicrobial protein RNase 7. In this study, we report that basal cells are the principal cell type producing RNase 7 in cultured primary bronchial epithelial cells (PBEC). Exposure of submerged cultured PBEC (primarily consisting of basal cells) to the respiratory pathogen nontypeable Haemophilus influenzae resulted in a marked increase in expression of RNase 7, although this was not observed in differentiated air-liquid interface cultured PBEC. However, transient epithelial injury in air-liquid interface-cultured PBEC induced by cigarette smoke exposure led to epidermal growth factor receptor-mediated expression of RNase 7 in remaining basal cells. The selective induction of RNase 7 in basal cells by cigarette smoke was demonstrated using confocal microscopy and by examining isolated luminal and basal cell fractions. Taken together, these findings demonstrate a phenotype-specific innate immune activity of airway epithelial basal cells, which serves as a second line of airway epithelial defense that is induced by airway epithelial injury.
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands; G.D.Amatngalim@lumc.nl.
authors.forename: Gimano D
authors.initials: GD
authors.lastname: Amatngalim
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands;
authors.forename: Yolanda
authors.initials: Y
authors.lastname: van Wijck
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands;
authors.forename: Yvonne
authors.initials: Y
authors.lastname: de Mooij-Eijk
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands;
authors.forename: Renate M
authors.initials: RM
authors.lastname: Verhoosel
authors.affiliation: Department of Dermatology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany; and.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Harder
authors.affiliation: Galapagos BV, 2333 CR Leiden, the Netherlands.
authors.forename: Annemarie N
authors.initials: AN
authors.lastname: Lekkerkerker
authors.affiliation: Galapagos BV, 2333 CR Leiden, the Netherlands.
authors.forename: Richard A J
authors.initials: RA
authors.lastname: Janssen
authors.affiliation: Department of Pulmonology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands;
authors.forename: Pieter S
authors.initials: PS
authors.lastname: Hiemstra
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D015870:Gene Expression; D006193:Haemophilus influenzae / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D008954:Models, Biological; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D012260:Ribonucleases / Q000096:biosynthesis* / Q000235:genetics; D012906:Smoke / Q000009:adverse effects
chemical_list: D012906:Smoke; D066246:ErbB Receptors; D012260:Ribonucleases; C470000:Ribonuclease 7