Inflammation and CFTR: might neutrophils be the key in cystic fibrosis?
The aim of this hypothesis is to provide new insights into the still unclear mechanisms governing airway inflammation in cystic fibrosis. Although the genetic basis of cystic fibrosis as well as the molecular structure of cystic fibrosis transmembrane regulator (CFTR), the mutated protein which causes the disease, have been well defined, a clear relationship between the genetic defect and the pulmonary pathophysiology, especially chronic infections and neutrophil-dominated airway inflammation has not been established. Cystic fibrosis is thus a unique pathological situation in that neutrophils can be depicted as both an antiinfectious and a proinflammatory cell. In cystic fibrosis there is an emerging picture of an imbalance between these two roles with both a reduction in the antiinfectious efficacy and an augmentation of the proinflammatory functions. Better knowledge of fundamental defects in neutrophil function in cystic fibrosis as well as a novel cellular function of CFTR, which will be reviewed, will allow identification of potentially new clinical targets and aid selective therapeutic action aimed at counteracting the lethal neutrophil-induced airway inflammation. The rationale for colchicine therapy is a significant example of a drug which might act both at the molecular levels on CFTR expression in epithelial cells and on neutrophils to mediate antiinflammatory effects. Preliminary results are presented in this issue (Med Inflamm 1999; 8: 13-15).
Witko-Sarsat
V
V
INSERM U507, Hôpital Necker Enfants-Malades, Paris, France.
Sermet-Gaudelus
I
I
Lenoir
G
G
Descamps-Latscha
B
B
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D003550:Cystic Fibrosis / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D009504:Neutrophils / Q000502:physiology*
D000893:Anti-Inflammatory Agents; C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator