mtMPs were procoagulant. (A) A dose-dependent acceleration of plasma clotting time induced by mtMPs and BDMPs (n = 3/point; repeated measures ANOVA, *P < .001 vs no microparticles). (B) This mtMP-induced coagulation was blocked by 200 nM lactadherin (n = 3/group; paired t test). (C) Plasma clotting induced by 25 μg/mL CL in the presence of increasing concentrations of lactadherin (n = 3; repeated measures ANOVA, * P < .01 vs no CL). Uninjured mice were injected with PBS, mtMPs, or BDMPs (both at 2.5 × 104/μL). Plasma samples were collected 30 minutes after injection to measure clotting time (D; n = 6/group; repeated measures ANOVA, *P < .01 vs PBS) and D-dimer (E; n = 6/group; repeated measures ANOVA, P < .01 vs PBS). (F) HE stain of the lungs from mtMP-injected mice shows erythrocyte accumulation in the extravascular space (*, top left) compared with PBS-injected mice (top right), and extensive fibrin deposition in the dilated pulmonary interstitial vessels (arrowheads, bottom left) compared with PBS-injected mice (top right). Microvascular fibrin-rich thrombosis is shown in the pulmonary vasculature (arrow, bottom right) of mtMP-injected mice. Images are representative of 6 mice/group.
