Neutrophil recruitment and airway epithelial cell involvement in chronic cystic fibrosis lung disease.
The pathological hallmark of cystic fibrosis (CF) chronic inflammatory response is the massive neutrophil influx into the airways. This dysregulated neutrophil emigration may be caused by the abnormal secretion of chemoattractants by respiratory epithelial cells and polarised lymphocyte T-helper response. Neutrophils from CF patients have a different response to inflammatory mediators than neutrophils from normal subjects, indicating that they are primed in vivo before entering the CF airways. CF neutrophils secrete more myeloperoxidase and elastase, mobilise less opsonin receptors and release less L-selectin than non-CF neutrophils. Moreover, they show altered cytokine production and a dysregulated chemotaxis response. Laboratory studies now suggest that CFTR is involved in regulating some neutrophil functions and indicate that altered properties of CF neutrophils may depend on genetic factors. Current gene therapy approaches are targeted to the respiratory epithelium, but many hurdles oppose an efficient and efficacious CFTR gene transfer. The possibility of CFTR gene therapy-based approach targeting CF neutrophils at the hematopoietic stem cell level is discussed.
Conese
Massimo
M
Institute for Experimental Treatment of Cystic Fibrosis, H.S. Raffaele, Milano, Italy. conese.massimo@hsr.it
Copreni
Elena
E
Di Gioia
Sante
S
De Rinaldis
Pietro
P
Fumarulo
Ruggiero
R
D001980:Bronchi / Q000503:physiopathology; D002465:Cell Movement / Q000502:physiology; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000503:physiopathology* / Q000628:therapy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D004848:Epithelium / Q000503:physiopathology; D015316:Genetic Therapy; D006801:Humans; D009504:Neutrophils / Q000502:physiology*
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator