TY - JOUR
T1 - Neutrophil survival-enhancing activity in sputum from patients with diffuse panbronchiolitis
AU - Nishimaki, Katsushi
AU - Nawata, Jun
AU - Okada, Shinji
AU - Hattori, Toshio
AU - Ohno, Isao
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/7
Y1 - 2005/7
N2 - Diffuse panbronchiolitis (DPB) is a life-threatening airway disease in which neutrophils persistently and massively emigrating to the airways cause progressive and irreversible tissue damage. However, the pathogenesis of the airway inflammation remains unclear. The failure of non-inflammatory removal of emigrating neutrophils due to delayed apoptosis has been proposed as a mechanism by which the neutrophilic inflammation persists. Therefore, we aimed to investigate whether an activity that delays neutrophil apoptosis is present at the inflamed sites in DPB. Neutrophils isolated from normal volunteers were cultured with sputum extracts of patients with DPB, and viability and apoptosis of neutrophil was evaluated for the culture period. Neutrophils cultured with sputum extracts for 2 and 3 days showed significantly enhanced survival compared to those with medium alone. The neutrophil survival-enhancing activity in sputum extracts was heat-labile and partially, but significantly, neutralized with anti-human GM-CSF, but not with anti-human G-CSF antibody. The enhancement of neutrophil survival was associated with an inhibition of apoptosis demonstrated by cytology, TUNEL assay and DNA fragmentation analysis. These results suggest that neutrophil apoptosis is prevented by survival-enhancing factors including GM-CSF in the airways of DPB, leading to neutrophil death by necrosis that causes further recruitment and activation of neutrophils.
AB - Diffuse panbronchiolitis (DPB) is a life-threatening airway disease in which neutrophils persistently and massively emigrating to the airways cause progressive and irreversible tissue damage. However, the pathogenesis of the airway inflammation remains unclear. The failure of non-inflammatory removal of emigrating neutrophils due to delayed apoptosis has been proposed as a mechanism by which the neutrophilic inflammation persists. Therefore, we aimed to investigate whether an activity that delays neutrophil apoptosis is present at the inflamed sites in DPB. Neutrophils isolated from normal volunteers were cultured with sputum extracts of patients with DPB, and viability and apoptosis of neutrophil was evaluated for the culture period. Neutrophils cultured with sputum extracts for 2 and 3 days showed significantly enhanced survival compared to those with medium alone. The neutrophil survival-enhancing activity in sputum extracts was heat-labile and partially, but significantly, neutralized with anti-human GM-CSF, but not with anti-human G-CSF antibody. The enhancement of neutrophil survival was associated with an inhibition of apoptosis demonstrated by cytology, TUNEL assay and DNA fragmentation analysis. These results suggest that neutrophil apoptosis is prevented by survival-enhancing factors including GM-CSF in the airways of DPB, leading to neutrophil death by necrosis that causes further recruitment and activation of neutrophils.
KW - Apoptosis
KW - Diffuse panbronchiolitis
KW - Neutrophils
KW - Sputum
KW - Survival
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U2 - 10.1016/j.rmed.2004.12.007
DO - 10.1016/j.rmed.2004.12.007
M3 - Article
C2 - 15939254
AN - SCOPUS:20444372996
VL - 99
SP - 910
EP - 917
JO - Respiratory Medicine
JF - Respiratory Medicine
SN - 0954-6111
IS - 7
ER -