Synergy between a plasminogen cascade and MMP-9 in autoimmune disease
J. Clin. Invest. Zhi Liu, et al. 115:879 doi:10.1172/JCI23977 [Go to this article.]

Figure 6
Functional relationship between plasmin, MMP-9, NE, and α1-PI in experimental BP. +/+, MMP-9^–/–, Plg^–/–, and tuPA^–/– mice (n = 6) were injected with anti-mBP180 IgG and examined 4 hours and 12 hours later. (A) Plasmin activity assay showed similar levels of tissue plasmin activity in +/+ and MMP-9^–/– mice at 4 hours but significantly higher levels of tissue plasmin activity in the lesional skin of +/+ (bar 5) mice compared with MMP-9^–/– (bar 6), Plg^–/– (bar 7), and tuPA^–/– (bar 8) mice at 12 hours. (B) MMP colorimetric assay revealed increased levels of MMP activity in lesional skin of +/+ mice (bars 1 and 5) as compared with those in nonlesional skin of MMP-9^–/– (bars 2 and 6), Plg^–/– (bars 3 and 7), and tuPA^–/– (bars 4 and 8) mice. (C) NE activity was significantly higher in the lesional skin of +/+ mice (bars 1 and 5) relative to MMP-9^–/– (bars 2 and 6), Plg^–/– (bars 3 and 7), and tuPA^–/– (bars 4 and 8) mice. (D) NE inhibition assay showed a significantly reduced level of α1-PI in the lesional skin of +/+ mice (bars 1 and 5) as compared with the skin of MMP-9^–/– (bars 2 and 6), Plg^–/– (bars 3 and 7), and tuPA^–/– (bars 4 and 8) mice. *P < 0.05 and **P < 0.001 for paired samples. (E–H) Plg^–/– mice, when reconstituted locally with 5 × 10⁵ neutrophils from +/+ (F), Plg^–/– (G), or MMP-9^–/– (H) mice, developed BP blisters 12 hours after pathogenic IgG injection. n = 6.