title: Inflammatory response of tracheobronchial epithelial cells to endotoxin.
abstract: Respiratory epithelial cells play a crucial role in the inflammatory response in endotoxin-induced lung injury, an experimental model for acute lung injury. To determine the role of epithelial cells in the upper respiratory compartment in the inflammatory response to endotoxin, we exposed tracheobronchial epithelial cells (TBEC) to lipopolysaccharide (LPS). Expression of inflammatory mediators was analyzed, and the biological implications were assessed using chemotaxis and adherence assays. Epithelial cell necrosis and apoptosis were determined to identify LPS-induced cell damage. Treatment of TBEC with LPS induced enhanced protein expression of cytokines and chemokines (increases of 235-654%, P < 0.05), with increased chemotactic activity regarding neutrophil recruitment. Expression of the intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was enhanced by 52-101% (P < 0.0001). This upregulation led to increased adhesion of neutrophils, with >95% adherence to TBEC after LPS stimulation, which could be blocked by either ICAM-1 (69%) or VCAM-1 antibodies (55%) (P < 0.05). Enhanced neutrophil-induced necrosis of TBEC was observed when TBEC were exposed to LPS. Reduced neutrophil adherence by ICAM-1 or VCAM-1 antibodies resulted in significantly lower TBEC death (52 and 34%, respectively, P < 0.05). Therefore, tight adherence of neutrophils to TBEC appears to promote epithelial cell killing. In addition to indirect effector cell-induced TBEC death, direct LPS-induced cell damage was seen with increased apoptosis rate in LPS-stimulated TBEC (36% increase of caspase-3, P < 0.01). These data provide evidence that LPS induces TBEC killing in a necrosis- and apoptosis-dependent manner.
authors.affiliation: Institute of Anesthesiology, University of Zurich Medical School, Zurich, Switzerland.
authors.forename: Simona B
authors.initials: SB
authors.lastname: Neff
authors.forename: Birgit Roth
authors.initials: BR
authors.lastname: Z'graggen
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Neff
authors.forename: Marina
authors.initials: M
authors.lastname: Jamnicki-Abegg
authors.forename: Dominik
authors.initials: D
authors.lastname: Suter
authors.forename: Ralph C
authors.initials: RC
authors.lastname: Schimmer
authors.forename: Christa
authors.initials: C
authors.lastname: Booy
authors.forename: Hana
authors.initials: H
authors.lastname: Joch
authors.forename: Thomas
authors.initials: T
authors.lastname: Pasch
authors.forename: Peter A
authors.initials: PA
authors.lastname: Ward
authors.forename: Beatrice
authors.initials: B
authors.lastname: Beck-Schimmer
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D001991:Bronchitis / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D002448:Cell Adhesion / Q000187:drug effects; D018925:Chemokines / Q000096:biosynthesis; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004731:Endotoxins / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D014136:Tracheitis / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D018925:Chemokines; D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1