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Thromb Haemost 2006; 95(04): 659-667
DOI: 10.1160/TH05-06-0405
Wound Healing and Inflammation/Infection
Schattauer GmbH

The effect of tissue type-plasminogen activator deletion and associated fibrin(ogen) deposition on macrophage localization in peritoneal inflammation

Andrew D. Cook   *
1   Arthritis and Inflammation Research Centre, Department of Medicine, and Cooperative Research Centre for Chronic Inflammatory Diseases, The University of Melbourne, Parkville, Victoria, Australia
,
Ross Vlahos   *
1   Arthritis and Inflammation Research Centre, Department of Medicine, and Cooperative Research Centre for Chronic Inflammatory Diseases, The University of Melbourne, Parkville, Victoria, Australia
,
Christine M. Massa
1   Arthritis and Inflammation Research Centre, Department of Medicine, and Cooperative Research Centre for Chronic Inflammatory Diseases, The University of Melbourne, Parkville, Victoria, Australia
,
Emma L. Braine
1   Arthritis and Inflammation Research Centre, Department of Medicine, and Cooperative Research Centre for Chronic Inflammatory Diseases, The University of Melbourne, Parkville, Victoria, Australia
,
Jason C. Lenzo
1   Arthritis and Inflammation Research Centre, Department of Medicine, and Cooperative Research Centre for Chronic Inflammatory Diseases, The University of Melbourne, Parkville, Victoria, Australia
,
Amanda L. Turner
1   Arthritis and Inflammation Research Centre, Department of Medicine, and Cooperative Research Centre for Chronic Inflammatory Diseases, The University of Melbourne, Parkville, Victoria, Australia
,
Kerrie J. Way
1   Arthritis and Inflammation Research Centre, Department of Medicine, and Cooperative Research Centre for Chronic Inflammatory Diseases, The University of Melbourne, Parkville, Victoria, Australia
,
John A. Hamilton
1   Arthritis and Inflammation Research Centre, Department of Medicine, and Cooperative Research Centre for Chronic Inflammatory Diseases, The University of Melbourne, Parkville, Victoria, Australia
› Author AffiliationsFinancial support: This work was supported by a grant and a Senior Principal Research Fellowship (J.A.H.) from the National Health and Medical Research Council of Australia.
Further Information

Publication History

Received 10 June 2005

Accepted after resubmission 02 February 2006

Publication Date:
30 November 2017 (online)

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Summary

There are two plasminogen activators (PAs), urokinase type-PA (u-PA) and tissue type-PA (t-PA). While u-PA is considered to be involved in cellular migration and tissue remodeling and t-PA in fibrinolysis, this distinction is not always clear-cut. With the use of u-PA and t-PA gene deficient mice (u-PA-/and t-PA-/mice, respectively) we have assessed the role of each PA in acute peritonitis. The cellular infiltrate in both thioglycolateand antigen-induced peritoneal exudates was unaffected in u-PA-/mice; in contrast, in t-PA-/mice, the macrophage numbers, particularly of the Mac-1hi population, in the peritoneal cavity by day4 were significantly reduced compared to wild-type mice. However, examination of the peritoneal wall revealed in fact increased numbers of macrophages adhering on/in the cavity lining at all time points studied; in addition, increased fibrin(ogen) staining was observed for these mice. The reduced macrophage numbers in the peritoneal cavities of t-PA-/mice could be increased by administration of plasmin or t-PA prior to harvesting the thioglycolate-elicited exudates. These results suggest that t-PA and not u-PA is the PA controlling fibrinolysis in murine peritonitis. In its absence macrophages adhere to the accumulated fibrin(ogen) on/in the cavity wall lining, most likely via Mac-1 binding, thus affecting migration into and/or out of the peritoneal cavity. They also highlight the need to examine both the peritoneal cavity and wall in order to monitor accurately the extent of a peritoneal inflammatory reaction. Peritoneal inflammation in t-PA-/mice represents a useful model to study the progression of intra-abdominal adhesions during surgery and clinical peritonitis.

Keywords

Tissue type-plasminogen activator - fibrin(olysis) - peritonitis - macrophages - urokinase-type plasminogen activator

* These co-authors contributed equally.


 

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