Am. J. Respir. Cell Mol. Biol.,
Volume 25, Number 2, August, 2001 186-195
Small Molecular Weight Secretory Factors from Pseudomonas aeruginosa
Have Opposite Effects on IL-8 and RANTES Expression
by Human Airway Epithelial Cells
Kevin G.
Leidal,
Kimber L.
Munson,
and
Gerene M.
Denning
Department of Internal Medicine, Veterans Administration Medical Center, and University of Iowa, Iowa City, Iowa
Pseudomonas aeruginosa is an opportunistic human pathogen
that causes both an acute lung disease in patients with hospital-acquired pneumonia and a chronic lung disease in individuals with cystic fibrosis. Many of the pathophysiologic effects
of P. aeruginosa infection are due to factors secreted by the
bacterium. Conditioned media from cultures of P. aeruginosa
increased interleukin-8 expression and decreased regulated
on activation, normal T cells expressed and secreted (RANTES)
expression by human airway epithelial cells. Both of these activities were present in heat-treated, protease-treated, small
molecular weight fractions. The activities were not inhibited by polymyxin B and were not extracted into ethyl acetate,
suggesting that they were not due to endotoxin or autoinducer. Conversely, results from chloroform extractions and
studies with a phenazine-minus mutant suggested that the
blue pigment pyocyanin contributes to these activities when
present. In addition to the effects of small molecular weight
factors on cytokine expression, proteases in bacterial-conditioned media further decreased levels of RANTES. By altering
expression, release, and/or activity of inflammatory cytokines,
secretory factors from P. aeruginosa could disrupt the delicate
balance that constitutes the immune response to bacterial infection and thus could contribute to the lung damage that occurs in P. aeruginosa-infected airways.
Abbreviations: cystic fibrosis, CF; enzyme-linked immunosorbent assay,
ELISA; glycerol-alanine-conditioned medium, GACM; Hepes-buffered saline, HBS; high phosphate-conditioned medium, HPCM; interferon, IFN; interleukin, IL; lipopolysaccharide, LPS; supplemented M9-conditioned medium, MCM; messenger RNA, mRNA; nuclear factor, NF; normal human bronchial epithelial cells, NHBE; nitric oxide, NO; regulated on activation, normal T cells expressed and secreted, RANTES; RNase
protection assay, RPA; standard deviation, SD; tumor necrosis factor, TNF.
