PMN recruitment to small airway epithelial cells in response to cigarette smoke extract (694.8)

Abstract

Cigarette smoke causes airway inflammation and recruitment of inflammatory cells, requiring migration across the endothelial and epithelial cell barriers. We propose that increased platelet‐activating factor (PAF) production in the airways of smokers enhances inflammatory cell recruitment. Human small airway epithelial cells (HSAEC) incubated with cigarette smoke extract (CSE) demonstrated increased PAF accumulation that was inhibited when cells were pretreated with (S)‐bromoenol lactone ((S)‐BEL, inhibits calcium‐independent phospholipase A2β (iPLA2β). HSAEC incubated with CSE also showed a significant inhibition of PAF acetyl hydrolase (PAF‐AH, degrades PAF). This suggests that increased PAF accumulation is a combination of increased synthesis (iPLA2β activation) and decreased degradation (PAF‐AH inhibition). 舲舲Polymorphonuclear leukocyte (PMN) adherence to HSAEC was increased with CSE and inhibited when HSAEC were pretreated with (S)‐BEL or PMN were pretreated with Ginkgolide B to block the PAF receptor. CSE also increased PMN transmigration across HSAEC in a basolateral to apical direction.舲舲 Taken together, our data demonstrate that PMN accumulation in the airways of smokers depends on increased PAF accumulation in HSAEC and suggest that Ginkgo biloba is a potential therapy to manage airway inflammation.