Transepithelial exit of leucocytes: inflicting, reflecting or resolving airway inflammation?

Glucocorticoids induce the production of the chemoattractant CCL20 in airway epithelium

“…We and others have noted that the anti-inflammatory pharmacology of glucocorticoids may spare several inflammation-like, innate immunity events including plasma exudation and neutrophilia associated with airway infection and repair [8]. Supporting the possibility of a role of neutrophils in asthmatic airway defence, sputum numbers of these cells appear disconnected to other measures of airway inflammation in steroid-treated asthma [2,8]. Perhaps the glucocorticoid-induced expression of neutrophil attractants [1,6,7] is a functional innate immunity-enhancing effect.…”

“…Hence, in addition to CCL20, reported and discussed by ZIJLSTRA et al [1], corticosteroids may upregulate several neutrophil-active chemokines in asthmatic bronchi. Work from different laboratories demonstrates reduced lumen neutrophils along with bronchial wall neutrophilia in corticosteroid-treated patients (reviewed in [8]). In these cases, corticosteroid-induced neutrophil attractants [5,6] may have retained neutrophils in the bronchial wall, preventing their elimination by the transepithelial exit route [8].…”

‘To measure is to know’ (Lord Kelvin)

“…7 Discordant bronchial wall versus lumen granulocyte numbers can further be expected to occur depending on the phase of the inflammatory process. 8 For example, at resolution of airway inflammation, increasing numbers of eosinophils and neutrophils in the bronchial lumen have been recorded along with decreased cellularity of the bronchial wall. 8 Such observations constitute evidence that transepithelial exit is a clinically important mode of elimination of bronchial wall leucocytes.…”

“…8 For example, at resolution of airway inflammation, increasing numbers of eosinophils and neutrophils in the bronchial lumen have been recorded along with decreased cellularity of the bronchial wall. 8 Such observations constitute evidence that transepithelial exit is a clinically important mode of elimination of bronchial wall leucocytes. With eosinophils, in particular, significant elimination of bronchial wall cells occurs by migration across the epithelial lining, whether intact or deranged; this is in contrast with the current lack of compelling in vivo evidence for a role of apoptosis and phagocytosis of these cells.…”

Wogonin Induces Eosinophil Apoptosis and Attenuates Allergic Airway Inflammation

“…Eosinophil clearance in the lung can occur by transepithelial migration and mucociliary clearance (9) or by apoptosis (programmed cell death) and subsequent removal of apoptotic cells by surrounding cells, including macrophages, dendritic cells, and epithelial cells (10)(11)(12). The relative contribution of these two elimination pathways, as well as the role that eosinophil apoptosis may play in resolution of allergic inflammation in humans, remains controversial (13).…”