Destination Airway: Tracking Granulocytes in Asthma

http://dx.doi.org/10.1016/j.ebiom.2014.11.002 2352-3964/© 2014 The Author. Published by Elsevier B.V Asthma affects over 300 million people worldwide and its prevatance of different potential therapeutic targets. With several new theralence continues to rise. It is typically characterised by intermittent symptoms of breathlessness, cough and wheeze punctuated with asthma attacks together with variable airflow obstruction, which are more frequent and persistent in severe disease (Chung et al., 2014). Underpinning this clinical presentation is airway inflammation and remodelling (Hartley et al., 2014). Airway inflammation in asthma is typically eosinophilic in associationwith allergic sensitisation, particularly in thosewith early onset disease (Chung et al., 2014; Hartley et al., 2014). Allergen challenge is an established asthmamodelwith features of both an early, predominately mast cell mediated, and a late asthmatic response driven by a more complex inflammatory response characterised by eosinophilic inflammation. However, beyond allergic asthma there is an increasing recognition that the inflammatory response in asthma is more heterogeneous with both eosinophilic and neutrophilic inflammation mediated by a combination of Th1/Tc1, Th2 and Th17 cytokines. Importantly, these inflammatory profiles do not necessarily occur independently, but may co-exist to varying degrees within an individual over time. The aetiology of neutrophilic asthma is poorly understood and is likely in part due to effects of high dose corticosteroid therapy, exposure to pollutants and pathogens (Hartley et al., 2014). Although the cause of eosinophilic and neutrophilic inflammatory responses in an individual are not fully understood granulocyte trafficking has been studied extensively and the critical growth factors, cytokines, chemokines and adhesion molecules have been described that coordinate hematopoiesis, bonemarrow egression, adhesion to the endothelium, selective chemotaxis and survival in tissue (Hartley et al., 2014). Our understanding of granulocyte trafficking has underpinned the development of several biologic and small molecule therapies targeting granulocyte recruitment and survival in asthma including anti-IL5, antiCRTh2, anti-CCR3, and anti-CXCR2 (Chung et al., 2014; Hartley et al., 2014; Nair et al., 2012; Haldar et al., 2009; Ortega et al., 2014). It is therefore perhaps somewhat surprising that our knowledge of the dynamics of granulocyte trafficking in humans in both health and disease remains limited and that this lack of understanding not only impacts upon a more comprehensive insight into mechanisms of granulocyte migration, but also challenges our understanding of the relative impor-