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 1
The Plg/plasmin system is required for experimental BP. WT mice and mice deficient in different components of the Plg/plasmin system were injected i.d. with pathogenic anti-mBP180 IgG (R530) or control IgG and examined 12 hours later. (A–H) WT (A and B), tPA^–/– (E), and uPA^–/– (F), but not tuPA^–/– (G) or Plg^–/– (H) mice injected with pathogenic IgG developed subepidermal blisters. WT injected with control IgG showed no disease (C and D). Arrows indicate sites of basal keratinocytes. E, epidermis; D, dermis; V, blister vesicle. Magnification, ×200. Higher magnifications of H&E staining sections demonstrate infiltrating neutrophils in the dermis (insets). Arrowheads indicate neutrophils. Magnification, ×920. (I) Plasmin chromogenic assay showed significantly higher levels of plasmin activity in the lesional skin of WT (bar 1), tPA^–/– (bar 3), and uPA^–/– (bar 4) mice as compared with the nonlesional skin of control (bar 2), tuPA^–/– (bar 5), and Plg^–/– (bar 6) mice. Data shown are the mean ± SEM. n = 9 for each group; *P < 0.001 versus WT. (J) MPO activity assay at 12 hours after injection (black bars) showed significantly higher levels of PMN recruitment in the lesional skin of WT (bar 7), tPA^–/– (bar 9), and uPA^–/– (bar 10) mice as compared with tuPA^–/– (bar 11) and Plg^–/– (bar 12) mice. At 4 hours after injection (gray bars), all mice had similar numbers of infiltrating neutrophils. n = 9 for each group; *P < 0.001 versus WT.