Fig. (1).

PGP and HMGB1 in the CF airway. Two potential pathways that may link airway expression of PGP and HMGB1 are shown. (A): Neutrophils are recruited to the airway by inflammatory stimuli and eventually undergo necrosis. Release of HMGB1 during necrosis is accompanied by concurrent but independent activation of proteases MMP-9 and prolyl endopeptidase, each required for the generation of PGP. (B): Extracellular HMGB1 activates airway macrophages through a TLR and/or RAGE dependent pathway, resulting in the release of MMP-9 and prolyl endopeptidase and generation of PGP, which perpetuate the inflammatory process.