MIP-1β is associated with eosinophilic airway inflammation

Abstract

Introduction: We recently found that MIP-1b is elevated in BALF from eosinophilic pneumonia and is positively correlated with eosinophils in BALF. The underlying mechanisms of the association between eosinophils and MIP-1β in airway inflammation have not yet been fully elucidated. Aims: To elucidate the functional roles of MIP-1β in the regulation of eosinophilic airway inflammation. Methods: Expression of CCR5, a CC chemokine receptor against MIP-1β, was confirmed by flow cytometry and RT-PCR in purified human eosinophils. The effect of MIP-1β on eosinophil chemotaxis was then evaluated using the Boyden chamber system. MIP-1β release from human eosinophils was measured by ELISA. The effects of an anti-MIP-1β antibody upon eosinophilic airway inflammation were also evaluated in an ovalbumin-induced mouse model. Results: CCR5 was expressed in human eosinophils and MIP-1b exerted eosinophil chemoattractant activity to a lesser extent than eotaxin. In addition, IL-5 enhanced the release of MIP-1b from human eosinophils. Interestingly, treatment with a neutralizing antibody to MIP-1β restored not only eosinophilic infiltration in the airway but also airway hyperresponsiveness in an ovalbumin-induced eosinophilic airway inflammation mouse model. Conclusion: We demonstrated that MIP-1b has eosinophil chemoattractant activity and is released from activated eosinophils. The neutralizing effect of MIP-1β in an in vivo model may support the involvement of MIP-1β in eosinophilic airway inflammation.