4.6 Article

The role of plasminogen activator inhibitor type 1 in the inflammatory response to local tissue injury

Journal

JOURNAL OF THROMBOSIS AND HAEMOSTASIS
Volume 3, Issue 5, Pages 1018-1025

Publisher

BLACKWELL PUBL LTD
DOI: 10.1111/j.1538-7836.2005.01311.x

Keywords

PAI-1; acute phase response; inflammation

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Background: The plasma levels of the plasminogen activator-inhibitor type 1 (PAI-1) are consistently elevated in patients with sterile tissue injury, often accompanied by a systemic acute phase protein response. It remains unknown, however, whether and to what extent PAI-1 affects the host response to trauma. Methods and results: By using the wellestablished murine model of turpentine-induced tissue injury we compared local and systemic inflammatory responses in PAI- I gene-deficient (PAI-1(-/-)) and normal wild-type (Wt) mice. Subcutaneous turpentine injection elicited strong increases in PAI-1 protein concentration in plasma and at the site of injury, but not in liver. PAI-1 mRNA was locally increased and expressed mainly by macrophages and endothelial cells. PAI-1 deficiency greatly enhanced the early influx of neutrophils to the site of inflammation, which was associated with increased edema and necrosis at 8 h after injection. Furthermore, PAI-1(-/-) mice showed a reduced early interleukin (IL)-6 induction with subsequently lower acute phase protein levels and a much slower recovery of body weight loss. Conclusion: These findings suggest that PAI-1 is not merely a marker of tissue injury but plays a functional role in the local and systemic host response to trauma.

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