CF: New Roles for Neutrophils

Although cystic fibrosis is caused by a mutation in the cystic fibrosis transmembrane conductance regulator channel, disease progression is thought to stem primarily from pulmonary damage caused by elastase. The prevailing theory is that elastase is released from necrotic neutrophils that are recruited to the lungs and fail in the fight against bacterial infection. But new work published in theProceedings of the National Academy of Sciences by researchers at Stanford University School of Medicine instead suggests living, but dysfunctional, neutrophils are the primary source of lung-damaging elastase in cystic fibrosis.¹

Under the necrotic neutrophil theory, elastase is passively released from dying neutrophils, a process so far downstream toward pulmonary damage that it presents no obvious drug targets. Typical strategies to prevent damage rely either on antibiotics to target infection, which minimize neutrophil recruitment to the lungs in the first place, or on compounds that target elastase after its release. But bacteria in the lungs often develop resistance to antibiotics, and inhibiting extracellular elastase may be too far downstream of where the damage starts, resulting in a case of too little, too late...