Enhanced fibrinolysis protects against lung ischemia–reperfusion injury

The fibrinolytic system. This system is strictly regulated by plasminogen activators, plasminogen activator receptor, plasminogen activator inhibitors, and α2-antiplasmin.

Expression of PAI-1 and fibrin in the WT mice and PAI-1 KO mice. A, Expression of PAI-1 mRNA in WT and PAI-1 KO left lung as determined by real-time PCR. β-actin was used to normalize the PAI-1 mRNA expression. B, Western blot analysis of fibrin expression in the lung from WT-IR and PAI-1 KO IR mice. Fibrin concentration is substantially reduced in PAI-1 KO mice compared with WT mice.

Immunohistochemical staining of neutrophils and macrophages in mice lung. Cells stained red indicate neutrophils or migratory macrophage infiltration. All sections were counterstained lightly with hematoxylin for viewing negatively stained cells. A, D, and G are stained with anti-Mac-2 antibody, B, E, and H are stained with antineutrophils antibody and C, F, and I are stained with normal rat immunoglobulin G (IgG). All figures are 200× magnifications. The bar graph shows the analysis of positive immunostaining of neutrophils and macrophages in the left lung of sham, WT-IR, and PAI-1 KO IR groups. Data shown are the mean ± standard error values for each group.

Pulmonary compliance, pulmonary artery pressures, and airway resistance in the PAI-1 KO IR mice compared with the WT-IR and sham mice. These physiologic parameters show less IRI in the PAI-1 KO IR compared to WT-IR. A, Comparison of lung compliance in sham, PAI-1 KO IR, and WT-IR mice. B, Comparison of pulmonary artery (PA) pressure in sham, PAI-1 KO IR, and WT-IR mice. C, Comparison of airway resistance in sham, PAI-1 KO IR and WT-IR mice. Data shown are the mean ± standard error values for each group. All P values are included in graph.

Proinflammatory mediators in plasma and BAL of IR injured mice. A, ELISA analysis showing TNF-α and MCP-1 in the plasma of WT-IR and PAI-1 KO IR mice. B, ELISA analysis showing TNF-α, KC, and MIP-2 in BAL of WT-IR and PAI-1 KO IR mice. C, Analysis showing mRNA expression of TNF-α, MCP-1, MIP-2, and KC in the left lung of WT and PAI-1 KO mice as determined by real-time PCR. Data shown are the mean ± standard error values for each group.