Prolongation of neutrophil survival by the culture supernatant of Pseudomonas aeruginosa.
OBJECTIVE
The pathogenesis of airway inflammation in diffuse panbronchiolitis (DPB) is unknown. Neutrophil survival-enhancing activity, partially mediated by granulocyte-macrophage colony-stimulating factor (GM-CSF), has been shown in the sputum from DPB patients. This study investigated the mechanisms of GM-CSF expression in the airways of DPB patients. This involved examining the effects of mucoid Pseudomonas aeruginosa strains derived from chronically colonized patients with DPB on neutrophil survival and GM-CSF expression.


METHODS
Neutrophils from healthy subjects were cultured with the culture supernatants of P. aeruginosa isolated from sputum of DPB patients in the presence or absence of anti-GM-CSF and anti-GM-CSF receptor (alpha chain) antibodies, and viable neutrophils were counted daily. GM-CSF gene expression in neutrophils was evaluated by RT-PCR.


RESULTS
Neutrophils cultured with the culture supernatants showed significantly prolonged survival, compared with neutrophils cultured with the control broth. The neutrophil survival-enhancing activity in the culture supernatants was lost by heating. The enhanced survival of neutrophils was abolished in the presence of anti-GM-CSF and anti-GM-CSF receptor (alpha chain) antibodies. GM-CSF mRNA was detected in neutrophils cultured with the bacterial supernatants, but not in those with the control broth.


CONCLUSIONS
P. aeruginosa-derived factors (rich in proteins) stimulated neutrophils to synthesize GM-CSF, which enhanced neutrophil survival in an autocrine/paracrine fashion.
Nishimaki
Katsushi
K
Department of Respiratory and Infectious Diseases, Tohoku University Graduate School of Medicine, Sendai, Japan.
Okuyama
Kaori
K
Okada
Shinji
S
Hattori
Toshio
T
Takayanagi
Motoaki
M
Ohno
Isao
I
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology*; D001988:Bronchiolitis / Q000503:physiopathology*; D002470:Cell Survival; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011550:Pseudomonas aeruginosa; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016178:Granulocyte-Macrophage Colony-Stimulating Factor