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 5
Blocking plasmin activity abolishes experimental BP. To demonstrate that α2-AP treatment blocks plasmin activity and subsequent MMP-9 activation and blistering, WT mice were injected i.d. with pathogenic anti-mBP180 IgG (2.64 mg/g body weight) followed by local administration of PBS, the plasmin inhibitor α2-AP, or the neutrophil cathepsin G inhibitor α1-AC. Mice were examined at 12 hours after IgG injection. (A) Pathogenic anti-mBP180 IgG induced high levels of neutrophil infiltration and subepidermal blisters in +/+ mice (bar 1) and mice treated with α1-AC (bar 3) but not in mice treated with α2-AP (bar 2). n = 9; *P < 0.01. (B) Plasmin activity assay showed a significant reduction of tissue plasmin activity in the α2-AP–treated mice (bar 2) as compared with that in the PBS-treated (bar 1) and α1-AC–treated mice (bar 3). n = 8 for each group; **P < 0.001. (C) Zymography assay detected an actMMP-9 band in the skin of mice treated with PBS (lane 1) and α1-AC (lane 3) but not in the skin of mice treated with α2-AP (lane 2). MMP colorimetric assay revealed a significant reduction of active MMP levels in the skin samples of α2-AP–treated mice (bar 2) as compared with those in the lesional skin samples of PBS- (bar 1) and α1-AC–treated mice (bar 3). n = 8; ^#P < 0.05.