Recruitment of Inflammatory cells to the Lung is Dependent upon Platelet Activating Factor production in Smokers

Abstract

To recruit inflammatory cells to the airways, cells must move from the circulation across the endothelial and epithelial cell barriers. Platelet‐activating factor (PAF) is involved in transendothelial migration in several vascular beds. We hypothesize that an increase in PAF production and cell recruitment may exacerbate inflammatory disease in smokers. We incubated human lung microvascular endothelial cells (HMVEC‐L) with cigarette smoke extract (CSE). CSE (20 μg/ml) significantly inhibited PAF‐acetylhydrolase (PAF‐AH, hydrolyzes and inactivates PAF) activity after 12 hours of CSE incubation (2.1 ± 0.1 to 0.7 ± 0.1 nmol/mg protein/min, n=6, p<0.01). Inhibition of PAF‐AH resulted in increased PAF production (538 ± 60 to 1580 ± 241 dpm, n=6, p<0.01) and PMN adherence (14 ± 3 to 47 ± 3%, n=4, p<0.01). Pretreatment of PMN with the PAF receptor antagonist CV3988 (10μM for 10 min) resulted in complete inhibition of PMN adherence (0.4 ± 0.1, n=4, p<0.01). In the lung, PMN accumulation in the small airways represents one of the initial steps in inflammation and emphysema. In conclusion, these studies have shown that PAF likely plays a central role in the recruitment of inflammatory cells to the small airways of cigarette smokers via inactivation of PAF‐AH and may exacerbate or initiate inflammatory lung disease.