Abstract
Introduction: Leukotrienes are key inflammatory and contractile mediators in the human airway, while the importance of resolvins in the resolution of inflammation is increasingly apparent. However, the ability of resolvins to modulate bronchoconstriction is unknown.
Aim: To investigate whether resolvin D1 (RvD1) can modulate the constriction of isolated rat and human bronchioles induced by leukotriene D4 (LTD4) or the muscarinic agonist carbachol (CCh).
Method: Rat bronchioles (0.4 mm diameter) were isolated and mounted on a wire myograph, bathed in Krebs solution and continually gassed with 95% O2 and 5% CO2 under a resting tension of 1.5 g. Contractile responses to LTD4 (1 nM – 1 μM) and CCh (10 nM – 10 μM) were recorded in the absence or presence of RvD1 (10 nM). Human bronchioles from two lobectomy patients were similarly investigated.
Results: Dose-dependent constriction of rat bronchioles induced by LTD4 (EC50 8 nM, n=6) was abolished by RvD1 (EC50 >100 nM, p<0.0001, n=5; two-way ANOVA). RvD1 similarly inhibited LTD4-induced constriction in human bronchioles (EC50 >100 nM), compared with LTD4 alone (EC50 1.8 nM, n=2). In contrast, CCh-induced constriction in rat bronchioles was unaffected by RvD1 (n=6).
Conclusion: These results show for the first time that resolvin D1 is a potent and selective inhibitor of LTD4-induced, but not CCh-induced, constriction in rat and human airway smooth muscle. Resolvins may provide novel approaches to treating bronchoconstriction and inflammation in airway disease. (Funded by the Gerald Kerkut Charitable Trust).
- © 2013 ERS