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

Andrew D. Cook; Ross Vlahos; Christine M. Massa; Emma L. Braine; Jason C. Lenzo; Amanda L. Turner; Kerrie J. Way; John A. Hamilton

doi:10.1160/TH05-06-0405

Thrombosis and Haemostasis, Table of Contents

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^*

¹Arthritis and Inflammation Research Centre, Department of Medicine, and Cooperative Research Centre for Chronic Inflammatory Diseases, The University of Melbourne, Parkville, Victoria, Australia

,

Ross Vlahos^*

¹Arthritis 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

¹Arthritis 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

¹Arthritis 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

¹Arthritis 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

¹Arthritis 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

¹Arthritis 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

¹Arthritis and Inflammation Research Centre, Department of Medicine, and Cooperative Research Centre for Chronic Inflammatory Diseases, The University of Melbourne, Parkville, Victoria, Australia

› Author Affiliations

Abstract

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-1^hi 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

Full Text

References

References
1 Dano K, Andreasen PA, Grondahl-Hansen J. et al. Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res 1985; 44: 139-266.
2 Blasi F, Vassalli JD, Dano K. Urokinase-type plasminogen activator: proenzyme, receptor, and inhibitors. J Cell Biol 1987; 104: 801-4.
3 Saksela O, Rifkin DB. Cell-associated plasminogen activation: regulation and physiological functions. Annu Rev Cell Biol 1988; 04: 93-126.
4 Akassoglou K, Kombrinck KW, Degen JL. et al. Tissue plasminogen activator-mediated fibrinolysis protects against axonal degeneration and demyelination after sciatic nerve injury. J Cell Biol 2000; 149: 1157-66.
5 Carmeliet P, Bouche A, De Clercq C. et al. Biological effects of disruption of the tissue-type plasminogen activator, urokinase-type plasminogen activator, and plasminogen activator inhibitor-1 genes in mice. Ann NY Acad Sci 1995; 748: 367-81 discussion 81-2.
6 Busso N, Hamilton JA. Extravascular coagulation and the plasminogen activator/plasmin system in rheumatoid arthritis. Arthritis Rheum 2002; 46: 2268-79.
7 Cook AD, Braine EL, Campbell IK. et al. Differing roles for urokinase and tissue-type plasminogen activator in collagen-induced arthritis. Am J Pathol 2002; 160: 917-26.
8 Busso N, Peclat V, Van Ness K. et al. Exacerbation of antigen-induced arthritis in urokinase-deficient mice. J Clin Invest 1998; 102: 41-50.
9 Yang YH, Carmeliet P, Hamilton JA. Tissue-type plasminogen activator deficiency exacerbates arthritis. J Immunol 2001; 167: 1047-52.
10 Nelson DS. Reaction to antigens in vivo of the peritoneal macrophages of guinea-pigs with delayed type hypersensitivity. Effects of anticoagulants and other drugs. Lancet 1963; 02: 175-6.
11 Haskill S, Becker S. Disappearance and reappearance of resident macrophages: importance in C. parvum-induced tumoricidal activity. Cell Immunol 1985; 90: 179-89.
12 Barth MW, Hendrzak JA, Melnicoff MJ. et al. Review of the macrophage disappearance reaction. J Leukoc Biol 1995; 57: 361-7.
13 Carmeliet P, Schoonjans L, Kieckens L. et al. Physiological consequences of loss of plasminogen activator gene function in mice. Nature 1994; 368: 419-24.
14 Ploplis VA, French EL, Carmeliet P. et al. Plasminogen deficiency differentially affects recruitment of inflammatory cell populations in mice. Blood 1998; 91: 2005-9.
15 Ploplis VA, Castellino FJ. Gene targeting of components of the fibrinolytic system. Thromb Haemost 2002; 87: 22-31.
16 Leenen PJ, de Bruijn MF, Voerman JS. et al. Markers of mouse macrophage development detected by monoclonal antibodies. J Immunol Methods 1994; 174: 5-19.
17 Sudo T, Nishikawa S, Ogawa M. et al. Functional hierarchy of c-kit and c-fms in intramarrow production of CFU-M. Oncogene 1995; 11: 2469-76.
18 Cook AD, Braine EL, Hamilton JA. The phenotype of inflammatory macrophages is stimulus dependent: implications for the nature of the inflammatory response. J Immunol 2003; 171: 4816-23.
19 Cook AD, Braine EL, Hamilton JA. Stimulus-dependent requirement for granulocyte-macrophage colony-stimulating factor in inflammation. J Immunol 2004; 173: 4643-51.
20 Zhang ZG, Chopp M, Goussev A. et al. Cerebral microvascular obstruction by fibrin is associated with upregulation of PAI-1 acutely after onset of focal embolic ischemia in rats. J Neurosci 1999; 19: 10898-907.
21 Nelson DS, Boyden SV. The loss of macrophages from peritoneal exudates following the injection of antigens into guinea-pigs with delayed-type hypersensitivity. Immunology 1963; 06: 264-75.
22 Szaba FM, Smiley ST. Roles for thrombin and fibrin(ogen) in cytokine/chemokine production and macrophage adhesion in vivo . Blood 2002; 99: 1053-9.
23 Chapman Jr. HA, Vavrin Z, Hibbs Jr. JB. Coordinate expression of macrophage procoagulant and fibrinolytic activity in vitro and in vivo . J Immunol 1983; 130: 261-6.
24 Henderson RB, Hobbs JA, Mathies M. et al. Rapid recruitment of inflammatory monocytes is independent of neutrophil migration. Blood 2003; 102: 328-35.
25 Chan J, Leenen PJ, Bertoncello I. et al. Macrophage lineage cells in inflammation: characterization by colony-stimulating factor-1 (CSF-1) receptor (c-Fms), ER-MP58, and ER-MP20 (Ly-6C) expression. Blood 1998; 92: 1423-31.
26 Miller LJ, Schwarting R, Springer TA. Regulated expression of the Mac-1, LFA-1, p150,95 glycoprotein family during leukocyte differentiation. J Immunol 1986; 137: 2891-900.
27 Flick MJ, Du X, Witte DP. et al. Leukocyte engagement of fibrin(ogen) via the integrin receptor αMβ2/Mac-1 is critical for host inflammatory response in vivo . J Clin Invest 2004; 113: 1596-606.
28 Ciano PS, Colvin RB, Dvorak AM. et al. Macrophage migration in fibrin gel matrices. Lab Invest 1986; 54: 62-70.
29 Busuttil SJ, Ploplis VA, Castellino FJ. et al. A central role for plasminogen in the inflammatory response to biomaterials. J Thromb Haemost 2004; 02: 1798-805.
30 Ploplis VA, Carmeliet P, Vazirzadeh S. et al. Effects of disruption of the plasminogen gene on thrombosis, growth, and health in mice. Circulation 1995; 92: 2585-93.
31 Romer J, Bugge TH, Pyke C. et al. Plasminogen and wound healing. Nat Med 1996; 02: 725.
32 Melnicoff MJ, Horan PK, Morahan PS. Kinetics of changes in peritoneal cell populations following acute inflammation. Cell Immunol 1989; 118: 178-91.
33 Bellingan GJ, Caldwell H, Howie SE. et al. In vivo fate of the inflammatory macrophage during the resolution of inflammation: inflammatory macrophages do not die locally, but emigrate to the draining lymph nodes. J Immunol 1996; 157: 2577-85.
34 Cao C, Lawrence DA, Strickland DK. et al. A specific role of integrin Mac-1 in accelerated macrophage efflux to the lymphatics. Blood 2005; 106: 3234-41.
35 Leak LV. Interaction of mesothelium to intraperitoneal stimulation. I. Aggregation of peritoneal cells. Lab Invest 1983; 48: 479-91.
36 Hart PH, Vitti GF, Burgess DR. et al. Human monocytes can produce tissue-type plasminogen activator. J Exp Med 1989; 169: 1509-14.
37 Hart PH, Burgess DR, Vitti GF. et al. Interleukin-4 stimulates human monocytes to produce tissue-type plasminogen activator. Blood 1989; 74: 1222-5.
38 Soo KS, Northeast AD, Happerfield LC. et al. Tissue plasminogen activator production by monocytes in venous thrombolysis. J Pathol 1996; 178: 190-4.
39 Myrhe-Jensen O, Larsen SB, Astrup T. Fibrinolytic activity in serosal and synovial membranes. Rats, guinea pigs, and rabbits. Arch Pathol 1969; 88: 623-30.
40 Raftery AT. Regeneration of peritoneum: a fibrinolytic study. J Anat 1979; 129: 659-64.
41 Vipond MN, Whawell SA, Thompson JN. et al. Peritoneal fibrinolytic activity and intra-abdominal adhesions. Lancet 1990; 335: 1120-2.
42 Ellis H, Harrison W, Hugh TB. The healing of peritoneum under normal and pathological conditions. Br J Surg 1965; 52: 471-6.
43 Thompson JN, Paterson-Brown S, Harbourne T. et al. Reduced human peritoneal plasminogen activating activity: possible mechanism of adhesion formation. Br J Surg 1989; 76: 382-4.
44 Gervin AS, Puckett CL, Silver D. Serosal hypofibrinolysis. A cause of postoperative adhesions. Am J Surg 1973; 125: 80-8.
45 Buckman RF, Woods M, Sargent L. et al. A unifying pathogenetic mechanism in the etiology of intraperitoneal adhesions. J Surg Res 1976; 20: 1-5.
46 Hau T, Payne WD, Simmons RL. Fibrinolytic activity of the peritoneum during experimental peritonitis. Surg Gynecol Obstet 1979; 148: 415-8.
47 Thompson JN. Preventing adhesions. Lancet 1995; 346: 1382.