title: p120-catenin expressed in alveolar type II cells is essential for the regulation of lung innate immune response.
abstract: The integrity of the lung alveolar epithelial barrier is required for the gas exchange and is important for immune regulation. Alveolar epithelial barrier is composed of flat type I cells, which make up approximately 95% of the gas-exchange surface, and cuboidal type II cells, which secrete surfactants and modulate lung immunity. p120-catenin (p120; gene symbol CTNND1) is an important component of adherens junctions of epithelial cells; however, its function in lung alveolar epithelial barrier has not been addressed in genetic models. Here, we created an inducible type II cell-specific p120-knockout mouse (p120EKO). The mutant lungs showed chronic inflammation, and the alveolar epithelial barrier was leaky to (125)I-albumin tracer compared to wild type. The mutant lungs also demonstrated marked infiltration of inflammatory cells and activation of NF-κB. Intracellular adhesion molecule 1, Toll-like receptor 4, and macrophage inflammatory protein 2 were all up-regulated. p120EKO lungs showed increased expression of the surfactant proteins Sp-B, Sp-C, and Sp-D, and displayed severe inflammation after pneumonia caused by Pseudomonas aeruginosa compared with wild type. In p120-deficient type II cell monolayers, we observed reduced transepithelial resistance compared to control, consistent with formation of defective adherens junctions. Thus, although type II cells constitute only 5% of the alveolar surface area, p120 expressed in these cells plays a critical role in regulating the innate immunity of the entire lung.
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois.
authors.forename: Andreia Z
authors.initials: AZ
authors.lastname: Chignalia
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Vogel
authors.affiliation: Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Albert B
authors.initials: AB
authors.lastname: Reynolds
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois.
authors.forename: Dolly
authors.initials: D
authors.lastname: Mehta
authors.affiliation: Department of Anesthesiology, University of Illinois College of Medicine, Chicago, Illinois.
authors.forename: Randal O
authors.initials: RO
authors.lastname: Dull
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois; Department of Anesthesiology, University of Illinois College of Medicine, Chicago, Illinois.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Minshall
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois.
authors.forename: Asrar B
authors.initials: AB
authors.lastname: Malik
authors.affiliation: Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois; University of Illinois Cancer Center, Chicago, Illinois. Electronic address: yuruliu@uic.edu.
authors.forename: Yuru
authors.initials: Y
authors.lastname: Liu
mesh_terms: D056809:Alveolar Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002199:Capillary Permeability / Q000276:immunology; D051177:Catenins / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007113:Immunity, Innate / Q000276:immunology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011650:Pulmonary Alveoli / Q000276:immunology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000095002:Delta Catenin
chemical_list: D051177:Catenins; D000095002:Delta Catenin; C000722349:Ctnnd1 protein, mouse