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

Authors

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

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.