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

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...

Full description

Saved in:
Bibliographic Details
Published in:Journal of thrombosis and haemostasis Vol. 3; no. 5; pp. 1018 - 1025
Main Authors: RENCKENS, R., ROELOFS, J. J. T. H., DE WAARD, V., FLORQUIN, S., LIJNEN, H. R., CARMELIET, P., VAN DER POLL, T.
Format: Journal Article
Language:English
Published: Oxford, UK Blackwell Science Inc 01.05.2005
Subjects:
acute phase response
Acute-Phase Proteins - metabolism
Acute-Phase Reaction
Animals
Body Weight
Chemokines - metabolism
Dose-Response Relationship, Drug
Edema
Endothelium, Vascular - metabolism
Female
In Situ Hybridization
Inflammation
Interleukin-1 - biosynthesis
Interleukin-6 - biosynthesis
Interleukin-6 - metabolism
Macrophages - metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Necrosis
Neutrophils - metabolism
PAI‐1
Plasminogen Activator Inhibitor 1 - physiology
RNA, Messenger - metabolism
Time Factors
Turpentine - pharmacology
ISSN:1538-7933, 1538-7836, 1538-7836
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 well‐established murine model of turpentine‐induced tissue injury we compared local and systemic inflammatory responses in PAI‐1 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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/j.1538-7836.2005.01311.x