title: Antimicrobial activity of PLUNC protects against Pseudomonas aeruginosa infection.
abstract: Epithelial antimicrobial activity may protect the lung against inhaled pathogens. The bactericidal/permeability-increasing protein family has demonstrated antimicrobial activity in vitro. PLUNC (palate, lung, and nasal epithelium associated) is a 25-kDa secreted protein that shares homology with bactericidal/permeability-increasing proteins and is expressed in nasopharyngeal and respiratory epithelium. The objective of this study was to determine whether PLUNC can limit Pseudomonas aeruginosa infection in mice. Transgenic mice (Scgb1a1-hPLUNC) were generated in which human PLUNC (hPLUNC) was directed to the airway epithelium with the Scgb1a1 promoter. The hPLUNC protein (hPLUNC) was detected in the epithelium throughout the trachea and bronchial airways and in bronchoalveolar lavage fluid. Bronchoalveolar lavage fluid from transgenic mice exhibited higher antibacterial activity than that from wild type littermates in vitro. After in vivo P. aeruginosa challenge, Scgb1a1-hPLUNC transgenic mice displayed enhanced bacterial clearance. This was accompanied by a decrease in neutrophil infiltration and cytokine levels. More importantly, the overexpressed hPLUNC in Scgb1a1-hPLUNC transgenic mouse airway significantly enhanced mouse survival against P. aeruginosa-induced respiratory infection. These data indicate that PLUNC is a novel antibacterial protein that likely plays a critical role in airway epithelium-mediated innate immune response.
authors.affiliation: Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Lina
authors.initials: L
authors.lastname: Lukinskiene
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Susan D
authors.initials: SD
authors.lastname: Reynolds
authors.forename: Chad
authors.initials: C
authors.lastname: Steele
authors.forename: Barry R
authors.initials: BR
authors.lastname: Stripp
authors.forename: George D
authors.initials: GD
authors.lastname: Leikauf
authors.forename: Jay K
authors.initials: JK
authors.lastname: Kolls
authors.forename: Y Peter
authors.initials: YP
authors.lastname: Di
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D011552:Pseudomonas Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D014598:Uteroglobin / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; C485599:BPIFA1 protein, human; D006023:Glycoproteins; D018836:Inflammation Mediators; D010750:Phosphoproteins; C556389:SCGB1A1 protein, human; C556390:Scgb1a1 protein, mouse; D014598:Uteroglobin