Targeting neutrophil elastase in cystic fibrosis

Abstract

Background: Cystic fibrosis (CF) is a lethal hereditary disease characterised

Flagellin Induces Myeloid-Derived Suppressor Cells: Implications for Pseudomonas aeruginosa Infection in Cystic Fibrosis Lung Disease

“…The open question remains how P. aeruginosa is able to colonize and chronically infect the CF airways in the face of this activated antibacterial Th17 response, suggesting mechanisms that modulate and impair Th17 immunity in CF. Combining these views and our data on MDSCs into one unifying pathophysiological scenario, we propose the following regulatory loop: 1) P. aeruginosa induces MDSCs through a flagellin-mediated mechanism; 2) MDSCs dampen T cell proliferation and Th17 cell responses and thereby protect P. aeruginosa from T cell-mediated host defense; and 3) MDSCs downregulate neutrophil recruitment by inhibiting IL-17 release, thereby preventing tissue damage by the unbalanced release of neutrophil-derived proteases and oxidants (47). On the basis of our unexpected observation that an increase of MDSCs correlated with improved pulmonary function in P. aeruginosa-infected CF patients, we speculate that the MDSCmediated downregulation of Th17 responses dampens neutrophilic lung tissue damage and could therefore beneficially modulate the course of CF lung disease, a conception necessitating future investigations.…”

The role for neutrophil extracellular traps in cystic fibrosis autoimmunity

“…As a result, CF patients have recurrent respiratory bacterial infections, frequently involving Pseudomonas aeruginosa, which is detected in up to 85% of patients (6)(7)(8). Inevitably, persistent bacterial infection in CF patients leads to an influx of neutrophils into the lung that results in a state of chronic inflammation (9)(10)(11)(12). Despite this characteristic immunopathology, CF patients demonstrate great clinical variability in their lung manifestations, which cannot be predicted by the nature of the CFTR mutation or the extent of bacterial infection (11)(12)(13).…”

Diverse Activities for Proteinases in the Pathogenesis of Chronic Obstructive Pulmonary Disease

“…Secretory leukocyte peptidase inhibitor (SLPI) and elafin are naturally occurring antiproteinases with anti-NE activity whose roles in COPD are not fully eludicated but may have potential as future treatment options (140). A number of synthetic low molecular www.intechopen.com Chronic Obstructive Pulmonary Disease -Current Concepts and Practice 58 weight inhibitors have been developed and are potential therapeutic agents for COPD.…”