The role of airway macrophages in apoptotic cell clearance following acute and chronic lung inflammation

Grabiec, Aleksander M.; Hussell, Tracy

Some classes of medications widely used in the clinic for other indications also promote efferocytosis. The antibiotic azithromycin increases phagocytosis of apoptotic cells by human airway macrophages in vitro [21, 131] , and significant improvement of the efferocytic function of airway macrophages from COPD patients after oral treatment with azithromycin has been reported [28] . In light of recent evidence that azithromycin reduces the frequency of exacerbations in COPD patients [132] , it is tempting to speculate that at least part of the immunomodulatory activities of macrolide antibiotics can be attributed to their effects on apoptotic cell clearance. Similarly, PPARγ agonists, which are used as insulin sensitizers in diabetes mellitus, but also display broad antiinflammatory effects, promote efferocytosis by airway macrophages in vitro and ameliorate disease symptoms in animal models of pulmonary inflammation [133, 134] . Enhancement of apoptotic cell engulfment is also observed after treatment of macrophages from COPD patients with simvastatin [135] , a member of the statin family of cholesterol-lowering drugs, and retrospective studies suggested that statins might reduce the risk of COPD exacerbations and mortality [136, 137] . More recently however, in a large randomised clinical trial, simvastatin treatment had no effect on exacerbation rates in COPD patients [138] , though the efferocytic function of airway macrophages was not analysed in this study. It remains an open question if patients with COPD can be stratified to identify a subgroup of patients that responds to statin treatment and whether this is related to effects on apoptotic cell clearance.