Degradation of T-kininogen by cathepsin D and matrix metalloproteinases

Cathepsin D, matrix metalloproteinase (MMP)-2, MMP-3 (stromelysin), and MMP-9 were isolated from rat granulomatous tissues, HT1080 human fibrosarcoma cells and rheumatoid synovial cell CM. At acidic conditions, cathepsin D cleaved T-kininogen into small peptides and released Met-T-kinin-Leu (kinin precursor), but failed to release kinin. MMP-3 cleaved T-kininogen into a 57 kDa fragment as measured by SDS-PAGE and Western blot analysis using anti-T-kininogen antiserum. On the other hand, no degradation of T-kininogen occurred during incubation with MMP-2 or MMP-9100/1) at pH 7.5 for 7 h.