Pseudomonas aeruginosa induction of apoptosis in respiratory epithelial cells: Analysis of the effects of cystic fibrosis transmembrane conductance regulator dysfunction and bacterial virulence factors

S. Rajan, G. Cacalano, R. Bryan, A. J. Ratner, C. U. Sontich, A. Van Heerckeren, P. Davis, A. Prince

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

Airway epithelial cells can respond to infection by activating several signaling pathways. We examined the induction of apoptosis in response to Pseudomonas aeruginosa PAO1 in normal cells and several cystic fibrosis (CF) and corrected cell lines. Epithelial cells in monolayers with tight junctions, confirmed by apical ZO-1 staining demonstrated by confocal microscopy, were entirely resistant to PAO1-induced apoptosis. In contrast, cell lines such as 9HTEo- cells that do not form tight junctions were susceptible, with 50% of the population apoptotic after 6 h of exposure to PAO1. CF transmembrane conductance regulator (CFTR) dysfunction caused by different mechanisms (trafficking mutations, overexpression of the regulatory domain or antisense constructs) did not alter rates of apoptosis, nor were differences apparent in terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling detection of apoptotic airway cells from PAO1 infected cftr -/- or control mice. Bacterial expression of specific adhesins, complete lipopolysaccharide, and a functional type III secretion system were all necessary to evoke apoptosis even in susceptible epithelial cells. Unlike other mucosal surfaces, the airway epithelium is highly resistant to apoptosis, and this response is activated only when the appropriate epithelial conditions are present as well as fully virulent P. aeruginosa capable of coordinately expressing both adhesins and cytotoxins.

Original languageEnglish (US)
Pages (from-to)304-312
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume23
Issue number3
StatePublished - 2000
Externally publishedYes

Fingerprint

Cystic Fibrosis Transmembrane Conductance Regulator
Virulence Factors
Pseudomonas aeruginosa
Epithelial Cells
Apoptosis
Tight Junctions
Cells
Cell Line
DNA Nucleotidylexotransferase
Confocal microscopy
Cytotoxins
Biotin
Cystic Fibrosis
Confocal Microscopy
Labeling
Lipopolysaccharides
Monolayers
Epithelium
Staining and Labeling
Mutation

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology

Cite this

Pseudomonas aeruginosa induction of apoptosis in respiratory epithelial cells : Analysis of the effects of cystic fibrosis transmembrane conductance regulator dysfunction and bacterial virulence factors. / Rajan, S.; Cacalano, G.; Bryan, R.; Ratner, A. J.; Sontich, C. U.; Van Heerckeren, A.; Davis, P.; Prince, A.

In: American Journal of Respiratory Cell and Molecular Biology, Vol. 23, No. 3, 2000, p. 304-312.

Research output: Contribution to journalArticle

@article{c6a55092d4e549d68eb39d4fc07789bb,
title = "Pseudomonas aeruginosa induction of apoptosis in respiratory epithelial cells: Analysis of the effects of cystic fibrosis transmembrane conductance regulator dysfunction and bacterial virulence factors",
abstract = "Airway epithelial cells can respond to infection by activating several signaling pathways. We examined the induction of apoptosis in response to Pseudomonas aeruginosa PAO1 in normal cells and several cystic fibrosis (CF) and corrected cell lines. Epithelial cells in monolayers with tight junctions, confirmed by apical ZO-1 staining demonstrated by confocal microscopy, were entirely resistant to PAO1-induced apoptosis. In contrast, cell lines such as 9HTEo- cells that do not form tight junctions were susceptible, with 50{\%} of the population apoptotic after 6 h of exposure to PAO1. CF transmembrane conductance regulator (CFTR) dysfunction caused by different mechanisms (trafficking mutations, overexpression of the regulatory domain or antisense constructs) did not alter rates of apoptosis, nor were differences apparent in terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling detection of apoptotic airway cells from PAO1 infected cftr -/- or control mice. Bacterial expression of specific adhesins, complete lipopolysaccharide, and a functional type III secretion system were all necessary to evoke apoptosis even in susceptible epithelial cells. Unlike other mucosal surfaces, the airway epithelium is highly resistant to apoptosis, and this response is activated only when the appropriate epithelial conditions are present as well as fully virulent P. aeruginosa capable of coordinately expressing both adhesins and cytotoxins.",
author = "S. Rajan and G. Cacalano and R. Bryan and Ratner, {A. J.} and Sontich, {C. U.} and {Van Heerckeren}, A. and P. Davis and A. Prince",
year = "2000",
language = "English (US)",
volume = "23",
pages = "304--312",
journal = "American Journal of Respiratory Cell and Molecular Biology",
issn = "1044-1549",
publisher = "American Thoracic Society",
number = "3",

}

TY - JOUR

T1 - Pseudomonas aeruginosa induction of apoptosis in respiratory epithelial cells

T2 - Analysis of the effects of cystic fibrosis transmembrane conductance regulator dysfunction and bacterial virulence factors

AU - Rajan, S.

AU - Cacalano, G.

AU - Bryan, R.

AU - Ratner, A. J.

AU - Sontich, C. U.

AU - Van Heerckeren, A.

AU - Davis, P.

AU - Prince, A.

PY - 2000

Y1 - 2000

N2 - Airway epithelial cells can respond to infection by activating several signaling pathways. We examined the induction of apoptosis in response to Pseudomonas aeruginosa PAO1 in normal cells and several cystic fibrosis (CF) and corrected cell lines. Epithelial cells in monolayers with tight junctions, confirmed by apical ZO-1 staining demonstrated by confocal microscopy, were entirely resistant to PAO1-induced apoptosis. In contrast, cell lines such as 9HTEo- cells that do not form tight junctions were susceptible, with 50% of the population apoptotic after 6 h of exposure to PAO1. CF transmembrane conductance regulator (CFTR) dysfunction caused by different mechanisms (trafficking mutations, overexpression of the regulatory domain or antisense constructs) did not alter rates of apoptosis, nor were differences apparent in terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling detection of apoptotic airway cells from PAO1 infected cftr -/- or control mice. Bacterial expression of specific adhesins, complete lipopolysaccharide, and a functional type III secretion system were all necessary to evoke apoptosis even in susceptible epithelial cells. Unlike other mucosal surfaces, the airway epithelium is highly resistant to apoptosis, and this response is activated only when the appropriate epithelial conditions are present as well as fully virulent P. aeruginosa capable of coordinately expressing both adhesins and cytotoxins.

AB - Airway epithelial cells can respond to infection by activating several signaling pathways. We examined the induction of apoptosis in response to Pseudomonas aeruginosa PAO1 in normal cells and several cystic fibrosis (CF) and corrected cell lines. Epithelial cells in monolayers with tight junctions, confirmed by apical ZO-1 staining demonstrated by confocal microscopy, were entirely resistant to PAO1-induced apoptosis. In contrast, cell lines such as 9HTEo- cells that do not form tight junctions were susceptible, with 50% of the population apoptotic after 6 h of exposure to PAO1. CF transmembrane conductance regulator (CFTR) dysfunction caused by different mechanisms (trafficking mutations, overexpression of the regulatory domain or antisense constructs) did not alter rates of apoptosis, nor were differences apparent in terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling detection of apoptotic airway cells from PAO1 infected cftr -/- or control mice. Bacterial expression of specific adhesins, complete lipopolysaccharide, and a functional type III secretion system were all necessary to evoke apoptosis even in susceptible epithelial cells. Unlike other mucosal surfaces, the airway epithelium is highly resistant to apoptosis, and this response is activated only when the appropriate epithelial conditions are present as well as fully virulent P. aeruginosa capable of coordinately expressing both adhesins and cytotoxins.

UR - http://www.scopus.com/inward/record.url?scp=0033823601&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033823601&partnerID=8YFLogxK

M3 - Article

C2 - 10970820

AN - SCOPUS:0033823601

VL - 23

SP - 304

EP - 312

JO - American Journal of Respiratory Cell and Molecular Biology

JF - American Journal of Respiratory Cell and Molecular Biology

SN - 1044-1549

IS - 3

ER -