Tissue proteases convert CCL23 into potent monocyte chemoattractants in patients with chronic rhinosinusitis

Because trypsin-like serine proteases have a major role in the truncation of CCL23 in NPs and inhibitors of neutrophil elastase (SSR69071) and matrix metalloproteinases (MMPs; marimastat), which are known to cleave CCL23,8,9 did not block the truncation (Fig 1, C), we focused on the mast cell trypsin-like serine protease tryptase. Importantly, the CCR1 antagonist CCX8960 completely blocked NP-treated CCL23-dependent but not CCL2 (a CCR2 ligand)-dependent migration of THP-1 cells, indicating that truncation of CCL23 by NP extracts results in increased CCR1-dependent migration of THP-1 cells (see Fig E3, B). Because previously known active truncated forms of CCL23 are formed by N-terminal truncations, we initially assessed N-terminal protein sequences.