HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/1/L86    most recent 00391.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (13) Citing Articles via Google Scholar Google Scholar Articles by Neff, S. B. Articles by Beck-Schimmer, B. Search for Related Content PubMed PubMed Citation Articles by Neff, S. B. Articles by Beck-Schimmer, B.

Inflammatory response of tracheobronchial epithelial cells to endotoxin

¹Institute of Anesthesiology and ²Institute of Physiology, University of Zurich Medical School, Zurich, Switzerland; ³Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan; ⁴Department of Surgery and ⁵Cardiovascular Research, Institute of Physiology, University of Zurich Medical School, Zurich, Switzerland

Submitted 21 October 2004 ; accepted in final form 8 August 2005

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.

lipopolysaccharide; inflammatory mediators; leukocytes

This article has been cited by other articles:

				S. Kim and J. A. Nadel Fibrinogen binding to ICAM-1 promotes EGFR-dependent mucin production in human airway epithelial cells Am J Physiol Lung Cell Mol Physiol, July 1, 2009; 297(1): L174 - L183. [Abstract] [Full Text] [PDF]

				R. MacRedmond, G. K. Singhera, and D. R. Dorscheid Erythropoietin inhibits respiratory epithelial cell apoptosis in a model of acute lung injury Eur. Respir. J., June 1, 2009; 33(6): 1403 - 1414. [Abstract] [Full Text] [PDF]

				P. S. Tang, M. Mura, R. Seth, and M. Liu Acute lung injury and cell death: how many ways can cells die? Am J Physiol Lung Cell Mol Physiol, April 1, 2008; 294(4): L632 - L641. [Abstract] [Full Text] [PDF]

				D. McClenahan, K. Hellenbrand, D. Atapattu, N. Aulik, D. Carlton, A. Kapur, and C. Czuprynski Effects of Lipopolysaccharide and Mannheimia haemolytica Leukotoxin on Bovine Lung Microvascular Endothelial Cells and Alveolar Epithelial Cells Clin. Vaccine Immunol., February 1, 2008; 15(2): 338 - 347. [Abstract] [Full Text] [PDF]

				T. A. Russo, Z. Wang, B. A. Davidson, S. A. Genagon, J. M. Beanan, R. Olson, B. A. Holm, P. R. Knight 3rd, P. R. Chess, and R. H. Notter Surfactant dysfunction and lung injury due to the E. coli virulence factor hemolysin in a rat pneumonia model Am J Physiol Lung Cell Mol Physiol, March 1, 2007; 292(3): L632 - L643. [Abstract] [Full Text] [PDF]

				F. Idali, M. Wiken, J. Wahlstrom, H. Mellstedt, A. Eklund, H. Rabbani, and J. Grunewald Reduced Th1 response in the lungs of HLA-DRB1*0301 patients with pulmonary sarcoidosis. Eur. Respir. J., March 1, 2006; 27(3): 451 - 459. [Abstract] [Full Text] [PDF]