Resolution of cell-mediated airways diseases

Abstract

"Inflammation resolution" has of late become a topical research area. Activation of resolution phase mechanisms, involving select post-transcriptional regulons, transcription factors, 'autacoids', and cell phenotypes, is now considered to resolve inflammatory diseases. Critical to this discourse on resolution is the elimination of inflammatory cells through apoptosis and phagocytosis. For major inflammatory diseases such as asthma and COPD we propose an alternative path to apoptosis for cell elimination. We argue that transepithelial migration of airway wall leukocytes, followed by mucociliary clearance, efficiently and non-injuriously eliminates pro-inflammatory cells from diseased airway tissues. First, it seems clear that numerous infiltrated granulocytes and lymphocytes can be speedily transmitted into the airway lumen without harming the epithelial barrier. Then there are a wide range of 'unexpected' findings demonstrating that clinical improvement of asthma and COPD is not only associated with decreasing numbers of airway wall inflammatory cells but also with increasing numbers of these cells in the airway lumen. Finally, effects of inhibition of transepithelial migration support the present hypothesis. Airway inflammatory processes have thus been much aggravated when transepithelial exit of leukocytes has been inhibited. In conclusion, the present hypothesis highlights risks involved in drug-induced inhibition of transepithelial migration of airway wall leukocytes. It helps interpretation of common airway lumen data, and suggests approaches to treat cell-mediated airway inflammation.

Airway inflammatory responses to diesel exhaust in allergic rhinitics

“…DE exposure induced a decrease in mast cell staining in the epithelium. This could reflect either: (a) a mast cell migration from the epithelium to the airway lumen (Persson & Uller, 2010) or to lymph nodes (Dabak et al, 2004) or (b) a degranulation of tryptase from mast cells (Amin, 2012). However, there were no increases in mast cell numbers detected in airway lavages and no other signs of an aggravated allergic inflammation, such as airway eosinophilia, allergic symptoms or increased airway permeability (measured as BW albumin).…”

Impact of emerging pollutants on pulmonary inflammation in asthmatic rats: ethanol vapors and agglomerated TiO2nanoparticles

“…Also, rats are reported to be more sensitive than mice to the pulmonary toxic effects induced by nano-TiO 2 (Bermudez et al, 2002). We have considered the possibility, as suggested by Persson & Uller (2010), that inflammatory cells might persist in the lung interstitium during lung disease/ injury instead of migrating towards the airway lumen, therefore decreasing the number of leukocytes found in BAL fluid. However this hypothesis was rejected following lung histology analyses, which showed that the level of inflammation in the lungs was proportional to BAL cellular results.…”

Authors' response

“…We repeat this cautionary note in an extended review on resolution of cell-mediated respiratory diseases where we discuss a role of egression in the elimination not only of granulocytes and lymphocytes but also of mast cells and dendritic cells 2. We further discuss how elimination of leucocytes through egression can be compatible with the use of sputum cell counts to adjust treatment in asthma 1.…”