Effect of Formoterol on Eosinophil Trans-Basement Membrane Migration Induced by Interleukin-8-Stimulated Neutrophils

Abstract

Background: Neutrophils are often increased in the airways of either chronic severe asthma or acute exacerbations. Neutrophils that have migrated in response to interleukin-8 (IL-8) may lead eosinophils to accumulate in the airways of patients with asthma and possibly aggravate the disease. In this study, we investigated whether formoterol modified the trans-basement membrane migration (TBM) of eosinophils stimulated with neutrophils and IL-8. Methods: Neutrophils and eosinophils were isolated from peripheral blood obtained from healthy donors. Eosinophil TBM was examined using a modified Boyden's chamber technique. Neutrophils were preincubated with or without formoterol (0.1 μ<smlcap>M</smlcap>) at 37°C for 30 min. Eosinophils were added to the upper compartment of a chamber with a Matrigel-coated transwell insert. Medium containing preincubated neutrophils and IL-8 was added to the lower compartment of the chamber. After a 90-minute incubation, the eosinophils that had migrated into the lower chamber were calculated using eosinophil peroxidase assays. Results: A combination of neutrophils and IL-8 significantly induced the eosinophil TBM; formoterol alone had no effect. However, formoterol modestly but significantly attenuated the TBM of eosinophils stimulated with neutrophils and IL-8. Conclusion: These results suggest that formoterol may act as a therapeutic agent on enhanced eosinophilic inflammation in acute exacerbation or persistent, severe asthma. The effect of formoterol likely involves the inhibition of neutrophil activation.

Pathological Roles of Neutrophil-Mediated Inflammation in Asthma and Its Potential for Therapy as a Target

“…Theophylline inhibits neutrophil chemotaxis [ 136 ] and reverses corticosteroid resistance [ 137 ]. Long-acting beta-agonists (LABA) mitigate the inflammatory reaction mediated by eosinophils and neutrophils by inhibiting IL-8 production [ 138 , 139 ]. Leukotriene receptor antagonists inhibit superoxide generation and the production of LTB-4 [ 140 ].…”

YCG063 inhibits Pseudomonas aeruginosa LPS-induced inflammation in human retinal pigment epithelial cells through the TLR2-mediated AKT/NF-κB pathway and ROS-independent pathways

“…Monocyte chemotactic protein-1 (MCP-1), a member of the C-C subfamily of chemokines, may elicit its inflammatory effect, leading to leukocyte accumulation and activation in areas of injury and inflammation under pathological and physiological conditions (19)(20)(21). IL-8, a member of the C-X-C chemokines, is an important mediator of various acute and chronic infectious conditions that attract and activate neutrophils and eosinophils (22).…”