PT  - JOURNAL ARTICLE
AU  - Paola Basilico
AU  - Tiziana Patrizia Cremona
AU  - Charaf Benarafa
TI  - LSC 2014 abstract - Increased myelopoiesis induced by cigarette smoke transiently increases kinetics of lung bacterial clearance in mice
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - 480
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/480.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/480.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - Effective clearance of pulmonary bacterial infections requires a rapid mobilization of neutrophils from the bone marrow to the blood and to the infection site. Mice deficient in the neutrophil protease inhibitor serpinB1 (sB1-/-) have a defect in bacterial clearance associated with decreased neutrophil survival, bone marrow neutropenia and increased protease activity. Here we evaluated bacterial clearance from the lungs of mice exposed to cigarette smoke for 6 weeks (5h/day, 5days/week) in combination with dysregulated neutrophil protease activity (sB1-/- mice). Interestingly, sB1-/- mice exposed to cigarette smoke had an efficient clearance of lung P. aeruginosa (PAO1) when infected 24h after the last smoke exposure. Increased clearance kinetics were also observed in wild-type mice exposed to cigarette smoke and infected with P. aeruginosa as well as with S. pneumoniae (6B and 19F). Importantly, when mice were inoculated 2 and 6 weeks after smoking cessation, clearance kinetics returned to levels similar to mice never exposed to cigarette smoke. We found that neutrophil proliferation and counts in the bone marrow was increased following smoke exposure. Similarly, treatment of sB1-/- mice with G-CSF for 5 days also increased neutrophil numbers and was associated with an ameliorated bacterial clearance. Our findings indicate that cigarette smoke exposure dramatically but transiently accelerates the kinetics of P. aeruginosa and S. pneumoniae clearance in the lungs in part through systemic inflammation resulting in increased neutrophil production.