Fig. 9

Effect of nebulized scuPA and tPA treatments on detection of the plasminogen activators, αM/uPA complexes and d-dimers in plasma. The data shown were obtained from all animals in Group 2 and illustrated in a box plots (showing median with interquartile range). Temporal changes in the levels of uPA antigen (a, b) and “molecular cage” type αM/uPA complexes (d, e) in plasma of animals treated with 4 and 8 mg scuPA are illustrated, respectively. Levels of uPA antigen (a, b) in plasma of animals treated with 4 and 8 mg scuPA increase significantly over time (p < 0.001). Difference were more profound with higher levels for animals treated with scuPA at 8 mg compared with those treated with tPA (c) or scuPA (a) at 4 mg at each time point where samples were collected, while levels for the scuPA at 4 mg were not significantly different from those for tPA (c). There was no statistical significant difference between plasma levels of d-dimers (f), indicating comparable systemic fibrinolysis in all treatment groups. c Illustrates relatively low total tPA antigen levels including all animals from the Group2 4 mg (n = 5) subgroups. Data are presented as box plots (showing interquartile ranges). The concentrations of antigens were determined by ELISA assays designed to detect the human antigens (Molecular Innovations, Inc., MI). Levels of αM/uPA complexes were assessed by uPA amidolytic activity in the plasma in the presence of 100 nM human recombinant PAI-1, as described [24]. The concentration of d-dimer in plasma of ISIALI sheep (f) after vehicle, tPA or scuPA nebulized treatment was measured using sheep d-dimer (D2D) ELISA Kit (MyBioSource, CA) as described in “Methods”