The urokinase receptor system, a key regulator at the intersection between inflammation, immunity, and coagulation

Current Pharmaceutical Design

Volumn 17, Issue 19, 2011, Pages 1924-1943

  Del Rosso, Mario ^a,b   Margheri, Francesca ^a,b   Serratì, Simona ^a,b   Chillà, Anastasia ^a,b   Laurenzana, Anna ^a,b   Fibbi, Gabriella ^a,b  

^a UNIVERSITY OF FLORENCE   (Italy)

^b ISTITUTO TOSCANO TUMORI   (Italy)

Author keywords

Coagulation; Contact system; Immunity; Inflammation; uPA; uPAR

Indexed keywords

ANAPHYLATOXIN; BETA1 INTEGRIN; BLOOD CLOTTING FACTOR 10A; BLOOD CLOTTING FACTOR 11A; BLOOD CLOTTING FACTOR 12; BLOOD CLOTTING FACTOR 12A; BRADYKININ; CYTOKINE; EPIDERMAL GROWTH FACTOR RECEPTOR; FIBRIN; FIBRIN DEGRADATION PRODUCT; FIBRINOGEN; G PROTEIN COUPLED RECEPTOR; HIGH MOLECULAR WEIGHT KININOGEN; INTEGRIN; KALLIKREIN; MATRIX METALLOPROTEINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PLASMIN; PLASMINOGEN; PLASMINOGEN ACTIVATOR INHIBITOR 1; PREKALLIKREIN; PROTEIN KINASE B; SERINE PROTEINASE; THROMBIN; UROKINASE; UROKINASE RECEPTOR; VITRONECTIN;

ADAPTIVE IMMUNITY; ANGIOGENESIS; BLOOD CLOTTING; BLOOD VESSEL PERMEABILITY; CELL INTERACTION; CELL INVASION; CELL MIGRATION; CELL PROLIFERATION; COMPLEMENT ACTIVATION; COMPLEMENT SYSTEM; CYTOKINE PRODUCTION; DIAPEDESIS; DISSEMINATED INTRAVASCULAR CLOTTING; ENDOTHELIUM CELL; FIBRINOLYSIS; HEMOSTASIS; HUMAN; HYPOTENSION; IMMUNITY; INFECTION; INFLAMMATION; INFLAMMATORY CELL; INJURY; INNATE IMMUNITY; INTERNALIZATION; LEUKOCYTE ACTIVATION; MEDIATOR RELEASE; NATURAL KILLER CELL; NEUTROPHIL CHEMOTAXIS; NONHUMAN; PAIN; PHAGOCYTOSIS; PLASMINOGEN ACTIVATION; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN DEGRADATION; PROTEIN FOLDING; PROTEIN PROTEIN INTERACTION; REVIEW; VASODILATATION;

ANIMALS; BLOOD COAGULATION; HUMANS; IMMUNITY, INNATE; INFLAMMATION; RECEPTORS, UROKINASE PLASMINOGEN ACTIVATOR; UROKINASE-TYPE PLASMINOGEN ACTIVATOR;

EID: 80051720462     PISSN: 13816128     EISSN: 18734286     Source Type: Journal    
DOI: 10.2174/138161211796718189     Document Type: Review

References (186)

1. Mignatti P, Rifkin DB. Biology and biochemistry of proteinases in tumor invasion. Physiol Rev 1993; 73: 161-195.
2. Choong PF, Nadesapillai AP. Urokinase plasminogen activator system: a multifunctional role in tumor progression and metastasis. Clin Orthop Relat Res 2003: S46-S58.
3. Montuori N, Visconte V, Rossi G, Ragno P. Soluble and cleaved forms of the urokinase-receptor: degradation products or active molecules? Thromb Haemost 2005; 93: 192-198.
4. Mondino A, Blasi F. uPA and uPAR in fibrinolysis, immunity and pathology. Trends Immunol 2004; 25: 450-455.
5. Rijneveld AW, Levi M, Florquin S et al. Urokinase receptor is necessary for adequate host defense against pneumococcal pneumonia. J Immunol 2002; 168: 3507-3511.
6. Gong Y, Hart E, Shchurin A, Hoover-Plow J. Inflammatory macrophage migration requires MMP-9 activation by plasminogen in mice. J Clin Invest 2008; 118: 3012-3024.
7. Nykjaer A, Moller B, Todd RF, et al. Urokinase receptor. An activation antigen in human T lymphocytes. J Immunol 1994; 152: 505-516.
8. Bianchi E, Ferrero E, Fazioli F, et al. Integrin-dependent induction of functional urokinase receptors in primary T lymphocytes. J Clin Invest 1996; 98: 1133-1141.
9. Al-Atrash G, Kitson RP, Xue Y, et al. uPA and uPAR contribute to NK cell invasion through the extracellular matrix. Anticancer Res 2001; 21: 1697-1704.
10. Al-Atrash G, Shetty S, Idell S, et al. IL-2-mediated upregulation of uPA and uPAR in natural killer cells. Biochem Biophys Res Commun 2002; 292: 184-189.
11. del Rosso M, Fibbi G, Pucci M, et al. The plasminogen activation system in inflammation. Front Biosci 2008; 13: 4667-4686.
12. Gonias SL. Factor XII bridges coagulation and fibrinolysis again. Blood 115: 4979-4980.
13. Colman RW, Wu Y, Liu Y. Mechanisms by which cleaved kininogen inhibits endothelial cell differentiation and signalling. Thromb Haemost 104: 875-885.
14. Kaplan AP, Joseph K, Silverberg M. Pathways for bradykinin formation and inflammatory disease. J Allergy Clin Immunol 2002; 109: 195-209.
15. Cochrane CG, Griffin JH. Molecular assembly in the contact phase of the Hageman factor system. Am J Med 1979; 67: 657-664.
16. Colman RW. Activation of plasminogen by human plasma kallikrein. Biochem Biophys Res Commun 1969; 35: 273-279.
17. Mandle RJ, Jr., Kaplan AP. Hageman-factor-dependent fibrinolysis: generation of fibrinolytic activity by the interaction of human activated factor XI and plasminogen. Blood 1979; 54: 850-862.
18. Schousboe I, Feddersen K, Rojkjaer R. Factor XIIa is a kinetically favorable plasminogen activator. Thromb Haemost 1999; 82: 1041-1046.
19. Kluft C, Dooijewaard G, Emeis JJ. Role of the contact system in fibrinolysis. Semin Thromb Hemost 1987; 13: 50-68.
20. Maas C, Govers-Riemslag JW, Bouma B, et al. Misfolded proteins activate factor XII in humans, leading to kallikrein formation without initiating coagulation. J Clin Invest 2008; 118: 3208-3018.
21. Joseph K, Kaplan AP. Formation of bradykinin: a major contributor to the innate inflammatory response. Adv Immunol 2005; 86: 159-208.
22. Colman RW. Biologic activities of the contact factors in vivo-- potentiation of hypotension, inflammation, and fibrinolysis, and inhibition of cell adhesion, angiogenesis and thrombosis. Thromb Haemost 1999; 82: 1568-1577.
23. LaRusch GA, Mahdi F, Shariat-Madar Z, et al. Factor XII stimulates ERK1/2 and Akt through uPAR, integrins, and the EGFR to initiate angiogenesis. Blood 115: 5111-5120.
24. Skrzydlewska E, Sulkowska M, Koda M, Sulkowski S. Proteolyticantiproteolytic balance and its regulation in carcinogenesis. World J Gastroenterol 2005; 11: 1251-1266.
25. Collen D, Lijnen HR. Thrombolytic agents. Thromb Haemost 2005; 93: 627-630.
26. Blasi F, Carmeliet P. uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol 2002; 3: 932-943.
27. 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 N Y Acad Sci 1995; 748: 367-381; discussion 381-2.
28. Selvarajan S, Lund LR, Takeuchi T, et al. A plasma kallikreindependent plasminogen cascade required for adipocyte differentiation. Nat Cell Biol 2001; 3: 267-275.
29. del Rosso M, Fibbi G, Pucci M, et al. Multiple pathways of cell invasion are regulated by multiple families of serine proteases. Clin Exp Metastasis 2002; 19: 193-207.
30. Herren T, Swaisgood C, Plow EF. Regulation of plasminogen receptors. Front Biosci 2003; 8: d1-d8.
31. Kuiper J, Otter M, Rijken DC, van Berkel TJ. Characterization of the interaction in vivo of tissue-type plasminogen activator with liver cells. J Biol Chem 1988; 263: 18220-18224.
32. Fukao H, Ueshima S, Takaishi T, et al. Enhancement of tissue-type plasminogen activator (t-PA) activity by purified t-PA receptor expressed in human endothelial cells. Biochim Biophys Acta 1997; 1356: 111-120.
33. Verrall S, Seeds NW. Characterization of 125I-tissue plasminogen activator binding to cerebellar granule neurons. J Cell Biol 1989; 109: 265-271.
34. Vassalli JD, Baccino D, Belin D. A cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinase. J Cell Biol 1985; 100: 86-92.
35. Wei Y, Waltz DA, Rao N, et al. Identification of the urokinase receptor as an adhesion receptor for vitronectin. J Biol Chem 1994; 269: 32380-32388.
36. Hoyer-Hansen G, Behrendt N, Ploug M, et al. The intact urokinase receptor is required for efficient vitronectin binding: receptor cleavage prevents ligand interaction. FEBS Lett 1997; 420: 79-85.
37. Sidenius N, Blasi F. Domain 1 of the urokinase receptor (uPAR) is required for uPAR-mediated cell binding to vitronectin. FEBS Lett 2000; 470: 40-46.
38. Sidenius N, Andolfo A, Fesce R, Blasi F. Urokinase regulates vitronectin binding by controlling urokinase receptor oligomerization. J Biol Chem 2002; 277: 27982-27990.
39. Kanse SM, Kost C, Wilhelm OG, et al. The urokinase receptor is a major vitronectin-binding protein on endothelial cells. Exp Cell Res 1996; 224: 344-353.
40. Deng G, Curriden SA, Wang S, et al. Is plasminogen activator inhibitor- 1 the molecular switch that governs urokinase receptormediated cell adhesion and release? J Cell Biol 1996; 134: 1563-1571.
41. Asakura S, Yang W, Sottile J, et al. Opposing effects of low and high molecular weight kininogens on cell adhesion. J Biochem 1998; 124: 473-484.
42. Colman RW, Pixley RA, Najamunnisa S, et al. Binding of high molecular weight kininogen to human endothelial cells is mediated via a site within domains 2 and 3 of the urokinase receptor. J Clin Invest 1997; 100: 1481-1487.
43. Chavakis T, Kanse SM, Lupu F, et al. Different mechanisms define the antiadhesive function of high molecular weight kininogen in integrin- and urokinase receptor-dependent interactions. Blood 2000; 96: 514-522.
44. Ossowski L, Aguirre-Ghiso JA. Urokinase receptor and integrin partnership: coordination of signaling for cell adhesion, migration and growth. Curr Opin Cell Biol 2000; 12: 613-620.
45. Xue W, Kindzelskii AL, Todd RF, Petty HR. Physical association of complement receptor type 3 and urokinase-type plasminogen activator receptor in neutrophil membranes. J Immunol 1994; 152: 4630-4640.
46. Reinartz J, Schafer B, Batrla R, et al. Plasmin abrogates alpha v beta 5-mediated adhesion of a human keratinocyte cell line (HaCaT) to vitronectin. Exp Cell Res 1995; 220: 274-282.
47. Wei Y, Lukashev M, Simon DI, et al. Regulation of integrin function by the urokinase receptor. Science 1996; 273: 1551-1555.
48. Xue W, Mizukami I, Todd RF, Petty HR. Urokinase-type plasminogen activator receptors associate with beta1 and beta3 integrins of fibrosarcoma cells: dependence on extracellular matrix components. Cancer Res 1997; 57: 1682-1689.
49. Margheri F, Manetti M, Serrati S, et al. Domain 1 of the urokinasetype plasminogen activator receptor is required for its morphologic and functional, beta2 integrin-mediated connection with actin cytoskeleton in human microvascular endothelial cells: failure of association in systemic sclerosis endothelial cells. Arthritis Rheum 2006; 54: 3926-3938.
50. Chaurasia P, Aguirre-Ghiso JA, Liang OD, et al. A region in urokinase plasminogen receptor domain III controlling a functional association with alpha5beta1 integrin and tumor growth. J Biol Chem 2006; 281: 14852-14863.
51. Tarui T, Mazar AP, Cines DB, Takada Y. Urokinase-type plasminogen activator receptor (CD87) is a ligand for integrins and mediates cell-cell interaction. J Biol Chem 2001; 276: 3983-3990.
52. Loftus JC, Smith JW, Ginsberg MH. Integrin-mediated cell adhesion: the extracellular face. J Biol Chem 1994; 269: 25235-25238.
53. Zhang F, Tom CC, Kugler MC, et al. Distinct ligand binding sites in integrin alpha3beta1 regulate matrix adhesion and cell-cell contact. J Cell Biol 2003; 163: 177-188.
54. Yebra M, Parry GC, Stromblad S, et al. Requirement of receptorboundurokinase-type plasminogen activator for integrin alphavbeta5-directed cell migration. J Biol Chem 1996; 271: 29393-29399.
55. Yebra M, Goretzki L, Pfeifer M, Mueller BM. Urokinase-type plasminogen activator binding to its receptor stimulates tumor cell migration by enhancing integrin-mediated signal transduction. Exp Cell Res 1999; 250: 231-240.
56. Tarui T, Andronicos N, Czekay RP, et al. Critical role of integrin alpha 5 beta 1 in urokinase (uPA)/urokinase receptor (uPAR, CD87) signaling. J Biol Chem 2003; 278: 29863-29872.
57. Monaghan-Benson E, McKeown-Longo PJ. Urokinase-type plasminogen activator receptor regulates a novel pathway of fibronectin matrix assembly requiring Src-dependent transactivation of epidermal growth factor receptor. J Biol Chem 2006; 281: 9450-9459.
58. Wei Y, Czekay RP, Robillard L, et al. Regulation of alpha5beta1 integrin conformation and function by urokinase receptor binding. J Cell Biol 2005; 168: 501-511.
59. Aguirre Ghiso JA, Kovalski K, Ossowski L. Tumor dormancy induced by downregulation of urokinase receptor in human carcinoma involves integrin and MAPK signaling. J Cell Biol 1999; 147: 89-104.
60. Aguirre-Ghiso JA, Liu D, Mignatti A, et al. Urokinase receptor and fibronectin regulate the ERK(MAPK) to p38(MAPK) activity ratios that determine carcinoma cell proliferation or dormancy in vivo. Mol Biol Cell 2001; 12: 863-879.
61. Aguirre-Ghiso JA, Estrada Y, Liu D, Ossowski L. ERK(MAPK) activity as a determinant of tumor growth and dormancy; regulation by p38(SAPK). Cancer Res 2003; 63: 1684-1695.
62. Montuori N, Carriero MV, Salzano S, et al. The cleavage of the urokinase receptor regulates its multiple functions. J Biol Chem 2002; 277: 46932-46939.
63. Cao DJ, Guo YL, Colman RW. Urokinase-type plasminogen activator receptor is involved in mediating the apoptotic effect of cleaved high molecular weight kininogen in human endothelial cells. Circ Res 2004; 94: 1227-1234.
64. Resnati M, Guttinger M, Valcamonica S, et al. Proteolytic cleavage of the urokinase receptor substitutes for the agonist-induced chemotactic effect. EMBO J 1996; 15: 1572-1582.
65. Fazioli F, Resnati M, Sidenius N, et al. A urokinase-sensitive region of the human urokinase receptor is responsible for its chemotactic activity. EMBO J 1997; 16: 7279-7286.
66. Ragno P. The urokinase receptor: a ligand or a receptor? Story of a sociable molecule. Cell Mol Life Sci 2006; 63: 1028-1037.
67. Resnati M, Pallavicini I, Wang JM, et al. The fibrinolytic receptor for urokinase activates the G protein-coupled chemotactic receptor FPRL1/LXA4R. Proc Natl Acad Sci USA 2002; 99: 1359-1364.
68. de Paulis A, Montuori N, Prevete N, et al. Urokinase induces basophil chemotaxis through a urokinase receptor epitope that is an endogenous ligand for formyl peptide receptor-like 1 and -like 2. J Immunol 2004; 173: 5739-5748.
69. Gyetko MR, Todd RF, Wilkinson CC, Sitrin RG. The urokinase receptor is required for human monocyte chemotaxis in vitro. J Clin Invest 1994; 93: 1380-1387.
70. Furlan F, Orlando S, Laudanna C, et al. The soluble D2D3(88-274) fragment of the urokinase receptor inhibits monocyte chemotaxis and integrin-dependent cell adhesion. J Cell Sci 2004; 117: 2909-2916.
71. Liu D, Aguirre Ghiso J, Estrada Y, Ossowski L. EGFR is a transducer of the urokinase receptor initiated signal that is required for in vivo growth of a human carcinoma. Cancer Cell 2002; 1: 445-457.
72. Cunningham O, Andolfo A, Santovito ML, et al. Dimerization controls the lipid raft partitioning of uPAR/CD87 and regulates its biological functions. EMBO J 2003; 22: 5994-6003.
73. Hoyer-Hansen G, Ronne E, Solberg H, et al. Urokinase plasminogen activator cleaves its cell surface receptor releasing the ligandbinding domain. J Biol Chem 1992; 267: 18224-18229.
74. Plesner T, Behrendt N, Ploug M. Structure, function and expression on blood and bone marrow cells of the urokinase-type plasminogen activator receptor, uPAR. Stem Cells 1997; 15: 398-408.
75. Levi M, Schultz M, van der Poll T. Disseminated intravascular coagulation in infectious disease. Semin Thromb Hemost 36: 367-377.
76. Blasi F. Urokinase and urokinase receptor: a paracrine/autocrine system regulating cell migration and invasiveness. Bioessays 1993; 15: 105-111.
77. Abraham E, Gyetko MR, Kuhn K, et al. Urokinase-type plasminogen activator potentiates lipopolysaccharide-induced neutrophil activation. J Immunol 2003; 170: 5644-5651.
78. Cao D, Mizukami IF, Garni-Wagner BA, et al. Human urokinasetype plasminogen activator primes neutrophils for superoxide anion release. Possible roles of complement receptor type 3 and calcium. J Immunol 1995; 154: 1817-1829.
79. May AE, Kanse SM, Lund LR, et al. Urokinase receptor (CD87) regulates leukocyte recruitment via beta 2 integrins in vivo. J Exp Med 1998; 188: 1029-1037.
80. Gyetko MR, Sitrin RG, Fuller JA, et al. Function of the urokinase receptor (CD87) in neutrophil chemotaxis. J Leukoc Biol 1995; 58: 533-538.
81. Vaday GG, Lider O. Extracellular matrix moieties, cytokines, and enzymes: dynamic effects on immune cell behavior and inflammation. J Leukoc Biol 2000; 67: 149-159.
82. Gyetko MR, Sud S, Chen GH, et al. Urokinase-type plasminogen activator is required for the generation of a type 1 immune response to pulmonary Cryptococcus neoformans infection. J Immunol 2002; 168: 801-809.
83. Fibbi G, Ziche M, Morbidelli L, et al. Interaction of urokinase with specific receptors stimulates mobilization of bovine adrenal capillary endothelial cells. Exp Cell Res 1988; 179: 385-395.
84. Mignatti P, Rifkin DB. Nonenzymatic interactions between proteinases and the cell surface: novel roles in normal and malignant cell physiology. Adv Cancer Res 2000; 78: 103-157.
85. del Rosso M, Fibbi G, Schmitt M, Mignatti P. Proteases and extracellular environment. Thromb Haemost 2005; 93: 190-191.
86. del Rosso M, Fibbi G, Matucci Cerinic M. The urokinase-type plasminogen activator system and inflammatory joint diseases. Clin Exp Rheumatol 1999; 17: 485-498.
87. Hart PH, Vitti GF, Burgess DR, et al. Activation of human monocytes by granulocyte-macrophage colony-stimulating factor: increased urokinase-type plasminogen activator activity. Blood 1991; 77: 841-848.
88. Busso N, Hamilton JA. Extravascular coagulation and the plasminogen activator/plasmin system in rheumatoid arthritis. Arthritis Rheum 2002; 46: 2268-2279.
89. Leizer T, Cebon J, Layton JE, Hamilton JA. Cytokine regulation of colony-stimulating factor production in cultured human synovial fibroblasts: I. Induction of GM-CSF and G-CSF production by interleukin-1 and tumor necrosis factor. Blood 1990; 76: 1989-1996.
90. Gyetko MR, Sud S, Kendall T, et al. Urokinase receptor-deficient mice have impaired neutrophil recruitment in response to pulmonary Pseudomonas aeruginosa infection. J Immunol 2000; 165: 1513-1519.
91. Gyetko MR, Sud S, Sonstein J, et al. Antigen-driven lymphocyte recruitment to the lung is diminished in the absence of urokinasetype plasminogen activator (uPA) receptor, but is independent of uPA. J Immunol 2001; 167: 5539-5542.
92. Sillaber C, Baghestanian M, Hofbauer R, et al. Molecular and functional characterization of the urokinase receptor on human mast cells. J Biol Chem 1997; 272: 7824-7832.
93. Gyetko MR, Chen GH, McDonald RA, et al. Urokinase is required for the pulmonary inflammatory response to Cryptococcus neoformans. A murine transgenic model. J Clin Invest 1996; 97: 1818-1826.
94. Estreicher A, Muhlhauser J, Carpentier JL, et al. The receptor for urokinase type plasminogen activator polarizes expression of the protease to the leading edge of migrating monocytes and promotes degradation of enzyme inhibitor complexes. J Cell Biol 1990; 111: 783-792.
95. Kindzelskii AL, Laska ZO, Todd RF, Petty HR. Urokinasetype plasminogen activator receptor reversibly dissociates from complement receptor type 3 (alpha M beta 2' CD11b/CD18) during neutrophil polarization. J Immunol 1996; 156: 297-309.
96. Bohuslav J, Horejsi V, Hansmann C, et al. Urokinase plasminogen activator receptor, beta 2-integrins, and Src-kinases within a single receptor complex of human monocytes. J Exp Med 1995; 181: 1381-1390.
97. Lominadze D, Dean WL, Tyagi SC, Roberts AM. Mechanisms of fibrinogen-induced microvascular dysfunction during cardiovascular disease. Acta Physiol (Oxf) 198: 1-13.
98. Sitrin RG, Todd RF, Albrecht E, Gyetko MR. The urokinase receptor (CD87) facilitates CD11b/CD18-mediated adhesion of human monocytes. J Clin Invest 1996; 97: 1942-1951.
99. Simon DI, Rao NK, Xu H, et al. Mac-1 (CD11b/CD18) and the urokinase receptor (CD87) form a functional unit on monocytic cells. Blood 1996; 88: 3185-3194.
100. Simon DI, Wei Y, Zhang L, et al. Identification of a urokinase receptor- integrin interaction site. Promiscuous regulator of integrin function. J Biol Chem 2000; 275: 10228-10234.
101. Pluskota E, Soloviev DA, Plow EF. Convergence of the adhesive and fibrinolytic systems: recognition of urokinase by integrin alpha Mbeta 2 as well as by the urokinase receptor regulates cell adhesion and migration. Blood 2003; 101: 1582-1590.
102. Pluskota E, Soloviev DA, Bdeir K, et al. Integrin alphaMbeta2 orchestrates and accelerates plasminogen activation and fibrinolysis by neutrophils. J Biol Chem 2004; 279: 18063-18072.
103. Roelofs JJ, Rouschop KM, Teske GJ, et al. The urokinase plasminogen activator receptor is crucially involved in host defense during acute pyelonephritis. Kidney Int 2006; 70: 1942-1947.
104. Chavakis T, Kanse SM, Pixley RA, et al. Regulation of leukocyte recruitment by polypeptides derived from high molecular weight kininogen. FASEB J 2001; 15: 2365-2376.
105. Rijneveld AW, Florquin S, Bresser P, et al. Plasminogen activator inhibitor type-1 deficiency does not influence the outcome of murine pneumococcal pneumonia. Blood 2003; 102: 934-939.
106. Marchesi VT, Florey HW. Electron micrographic observations on the emigration of leucocytes. Q J Exp Physiol Cogn Med Sci 1960; 45: 343-348.
107. Bianchi E, Bender JR, Blasi F, Pardi R. Through and beyond the wall: late steps in leukocyte transendothelial migration. Immunol Today 1997; 18: 586-591.
108. Rosenberg GA. Matrix metalloproteinases in brain injury. J Neurotrauma 1995; 12: 833-842.
109. Muller WA. The role of PECAM-1 (CD31) in leukocyte emigration: studies in vitro and in vivo. J Leukoc Biol 1995; 57: 523-528.
110. Smith C. In: Liu JHaD Ed. Adhesion: Its Role in Inflammatory Disease. New York WH Freeman. 1992; 83-115.
111. Hurley J. Acute Inflammation. Baltimore: Williams & Wilkins; 1972.
112. Beutler BA. TLRs and innate immunity. Blood 2009; 113: 1399-1407.
113. Bianchi ME. DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 2007; 81: 1-5.
114. Degryse B, de Virgilio M. The nuclear protein HMGB1, a new kind of chemokine? FEBS Lett 2003; 553: 11-17.
115. Gasque P. Complement: a unique innate immune sensor for danger signals. Mol Immunol 2004; 41: 1089-1098.
116. Gyetko MR, Aizenberg D, Mayo-Bond L. Urokinase-deficient and urokinase receptor-deficient mice have impaired neutrophil antimicrobial activation in vitro. J Leukoc Biol 2004; 76: 648-656.
117. Hovius JW, Bijlsma MF, van der Windt GJ, et al. The urokinase receptor (uPAR) facilitates clearance of Borrelia burgdorferi. PLoS Pathog 2009; 5: e1000447.
118. Wiersinga WJ, Kager LM, Hovius JW, et al. Urokinase receptor is necessary for bacterial defense against pneumonia-derived septic melioidosis by facilitating phagocytosis. J Immunol 184: 3079-3086.
119. Pliyev BK, Arefieva TI, Menshikov MY. Urokinase receptor (uPAR) regulates complement receptor 3 (CR3)-mediated neutrophil phagocytosis. Biochem Biophys Res Commun 397: 277-282.
120. Ross GD. Role of the lectin domain of Mac-1/CR3 (CD11b/CD18) in regulating intercellular adhesion. Immunol Res 2002; 25: 219-227.
121. Kiessling R, Klein E, Wigzell H. Natural killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype. Eur J Immunol 1975; 5: 112-117.
122. Reyburn H, Mandelboim O, Vales-Gomez M, et al. Human NKcells: their ligands, receptors and functions. Immunol Rev 1997;155: 119-125.
123. Cerwenka A, Lanier LL. Natural killer cells, viruses and cancer. Nat Rev Immunol 2001; 1: 41-49.
124. Nykjaer A, Petersen CM, Moller B, et al. Identification and characterization of urokinase receptors in natural killer cells and T-cellderivedlymphokine activated killer cells. FEBS Lett 1992; 300: 13-17.
125. al-Atrash G, Kitson RP, Xue Y, Goldfarb RH. Cooperation of urokinase plasminogen activator and matrix metalloproteinases in NK cell invasion. In Vivo 2000; 14: 565-570.
126. Gellert GC, Goldfarb RH, Kitson RP. Physical association of uPAR with the alphaV integrin on the surface of human NK cells. Biochem Biophys Res Commun 2004; 315: 1025-1032.
127. Gellert GC, Kitson RP, Goldfarb RH. Urokinase-type plasminogen activator receptor crosslinking in an NK cell line increases integrin surface expression by the MAP kinase/ERK 1/2 signaling pathway. J Cell Biochem 2003; 89: 279-288.
128. Lash GE, Otun HA, Innes BA, et al. Interferon-gamma inhibits extravillous trophoblast cell invasion by a mechanism that involves both changes in apoptosis and protease levels. FASEB J 2006; 20: 2512-2518.
129. de Oliveira LG, Lash GE, Murray-Dunning C, et al. Role of interleukin 8 in uterine natural killer cell regulation of extravillous trophoblast cell invasion. Placenta 31: 595-601.
130. Naruse K, Lash GE, Bulmer JN, et al. The urokinase plasminogen activator (uPA) system in uterine natural killer cells in the placental bed during early pregnancy. Placenta 2009; 30: 398-404.
131. Kawahara T, Douglas DN, Lewis J, et al. Critical role of natural killer cells in the rejection of human hepatocytes after xenotransplantation into immunodeficient mice. Transpl Int 23: 934-943.
132. Sonoda KH, Nakamura T, Young HA, et al. NKT cell-derived urokinase-type plasminogen activator promotes peripheral tolerance associated with eye. J Immunol 2007; 179: 2215-222.
133. van den Broeck T, Stevenaert F, Taveirne S, et al. Ly49Edependent inhibition of natural killer cells by urokinase plasminogen activator. Blood 2008; 112: 5046-5051.
134. Cohen SD, Israel E, Spiess-Meier B, Wainberg MA. Plasminogen activator is an apparent lymphocyte mitogen. J Immunol 1981; 126: 1415-1420.
135. Gyetko MR, Libre EA, Fuller JA, et al. Urokinase is required for T lymphocyte proliferation and activation in vitro. J Lab Clin Med 1999; 133: 274-288.
136. Gyetko MR, Sud S, Chensue SW. Urokinase-deficient mice fail to generate a type 2 immune response following schistosomal antigen challenge. Infect Immun 2004; 72: 461-467.
137. Stonehouse TJ, Woodhead VE, Herridge PS, et al. Molecular characterization of U937-dependent T-cell co-stimulation. Immunology 1999; 96: 35-47.
138. Woodhead VE, Stonehouse TJ, Binks MH, et al. Novel molecular mechanisms of dendritic cell-induced T cell activation. Int Immunol 2000; 12: 1051-1061.
139. Higazi AA, El-Haj M, Melhem A, et al. Immunomodulatory effects of plasminogen activators on hepatic fibrogenesis. Clin Exp Immunol 2008; 152: 163-173.
140. Krem MM, Di Cera E. Evolution of enzyme cascades from embryonic development to blood coagulation. Trends Biochem Sci 2002; 27: 67-74.
141. Delvaeye M, Conway EM. Coagulation and innate immune responses: can we view them separately? Blood 2009; 114: 2367-2374.
142. Levi M, van der Poll T, Buller HR. Bidirectional relation between inflammation and coagulation. Circulation 2004; 109: 2698-2704.
143. Esmon CT. The impact of the inflammatory response on coagulation. Thromb Res 2004; 114: 321-327.
144. Opal SM, Esmon CT. Bench-to-bedside review: functional relationships between coagulation and the innate immune response and their respective roles in the pathogenesis of sepsis. Crit Care 2003; 7: 23-38.
145. Busso N, Chobaz-Peclat V, Hamilton J, et al. Essential role of platelet activation via protease activated receptor 4 in tissue factorinitiated inflammation. Arthritis Res Ther 2008; 10: R42.
146. Drake WT, Lopes NN, Fenton JW, Issekutz AC. Thrombin enhancement of interleukin-1 and tumor necrosis factor-alpha induced polymorphonuclear leukocyte migration. Lab Invest 1992; 67: 617-627.
147. Fujita T, Yamabe H, Shimada M, et al. Thrombin enhances the production of monocyte chemoattractant protein-1 and macrophage inflammatory protein-2 in cultured rat glomerular epithelial cells. Nephrol Dial Transplant 2008; 23: 3412-3417.
148. Wadgaonkar R, Somnay K, Garcia JG. Thrombin induced secretion of macrophage migration inhibitory factor (MIF) and its effect on nuclear signaling in endothelium. J Cell Biochem 2008; 105: 1279-1288.
149. Huber-Lang M, Sarma JV, Zetoune FS, et al. Generation of C5a in the absence of C3: a new complement activation pathway. Nat Med 2006; 12: 682-687.
150. Clark A, Weymann A, Hartman E, et al. Evidence for nontraditional activation of complement factor C3 during murine liver regeneration. Mol Immunol 2008; 45: 3125-3132.
151. Naldini A, Aarden L, Pucci A, et al. Inhibition of interleukin-12 expression by alpha-thrombin in human peripheral blood mononuclear cells: a potential mechanism for modulating Th1/Th2 responses. Br J Pharmacol 2003; 140: 980-986.
152. Feistritzer C, Riewald M. Endothelial barrier protection by activated protein C through PAR1-dependent sphingosine 1-phosphate receptor-1 crossactivation. Blood 2005; 105: 3178-3184.
153. Krupiczojc MA, Scotton CJ, Chambers RC. Coagulation signaling following tissue injury: focus on the role of factor Xa. Int J Biochem Cell Biol 2008; 40: 1228-1237.
154. Shpacovitch V, Feld M, Hollenberg MD, et al. Role of proteaseactivated receptors in inflammatory responses, innate and adaptive immunity. J Leukoc Biol 2008; 83: 1309-1322.
155. Sutherland MR, Friedman HM, Pryzdial EL. Herpes simplex virus type 1-encoded glycoprotein C enhances coagulation factor VIIa activity on the virus. Thromb Haemost 2004; 92: 947-955.
156. Richardson DL, Pepper DS, Kay AB. Chemotaxis for human monocytes by fibrinogen-derived peptides. Br J Haematol 1976; 32: 507-513.
157. Kay AB, Pepper DS, McKenzie R. The identification of fibrinopeptide B as a chemotactic agent derived from human fibrinogen. Br J Haematol 1974; 27: 669-677.
158. Flick MJ, Du X, Witte DP, et al. Leukocyte engagement of fibrin(ogen) via the integrin receptor alphaMbeta2/Mac-1 is critical for host inflammatory response in vivo. J Clin Invest 2004; 113: 1596-1606.
159. Gaffney PJ. Fibrin degradation products. A review of structures found in vitro and in vivo. Ann N Y Acad Sci 2001; 936: 594-610.
160. Loike JD, Sodeik B, Cao L, et al. CD11c/CD18 on neutrophils recognizes a domain at the N terminus of the A alpha chain of fibrinogen. Proc Natl Acad Sci USA 1991; 88: 1044-1048.
161. Olexa SA, Budzynski AZ, Doolittle RF, et al. Structure of fragment E species from human cross-linked fibrin. Biochemistry 1981; 20: 6139-6145.
162. Smiley ST, King JA, Hancock WW. Fibrinogen stimulates macrophage chemokine secretion through toll-like receptor 4. J Immunol 2001; 167: 2887-2894.
163. Perez RL, Roman J. Fibrin enhances the expression of IL-1 beta by human peripheral blood mononuclear cells. Implications in pulmonary inflammation. J Immunol 1995; 154: 1879-1887.
164. Qi J, Kreutzer DL. Fibrin activation of vascular endothelial cells. Induction of IL-8 expression. J Immunol 1995; 155: 867-876.
165. Harley SL, Sturge J, Powell JT. Regulation by fibrinogen and its products of intercellular adhesion molecule-1 expression in human saphenous vein endothelial cells. Arterioscler Thromb Vasc Biol 2000; 20: 652-658.
166. Szaba FM, Smiley ST. Roles for thrombin and fibrin(ogen) in cytokine/ chemokine production and macrophage adhesion in vivo. Blood 2002; 99: 1053-1059.
167. Adams RA, Schachtrup C, Davalos D, et al. Fibrinogen signal transduction as a mediator and therapeutic target in inflammation: lessons from multiple sclerosis. Curr Med Chem 2007; 14: 2925-2936.
168. Drew AF, Tucker HL, Liu H, et al. Crescentic glomerulonephritis is diminished in fibrinogen-deficient mice. Am J Physiol Renal Physiol 2001; 281: F1157-F1163.
169. Drew AF, Liu H, Davidson JM, et al. Wound-healing defects in mice lacking fibrinogen. Blood 2001; 97: 3691-3698.
170. Wilberding JA, Ploplis VA, McLennan L, et al. Development of pulmonary fibrosis in fibrinogen-deficient mice. Ann N Y Acad Sci 2001; 936: 542-548.
171. Palumbo JS, Potter JM, Kaplan LS, et al. Spontaneous hematogenous and lymphatic metastasis, but not primary tumor growth or angiogenesis, is diminished in fibrinogen-deficient mice. Cancer Res 2002; 62: 6966-6972.
172. Altieri DC, Agbanyo FR, Plescia J, et al. A unique recognition site mediates the interaction of fibrinogen with the leukocyte integrin Mac-1 (CD11b/CD18). J Biol Chem 1990; 265: 12119-12122.
173. Altieri DC, Plescia J, Plow EF. The structural motif glycine 190- valine 202 of the fibrinogen gamma chain interacts with CD11b/CD18 integrin (alpha M beta 2, Mac-1) and promotes leukocyte adhesion. J Biol Chem 1993; 268: 1847-1853.
174. Altieri DC, Duperray A, Plescia J, et al. Structural recognition of a novel fibrinogen gamma chain sequence (117-133) by intercellular adhesion molecule-1 mediates leukocyte-endothelium interaction. J Biol Chem 1995; 270: 696-699.
175. Farrell DH, Thiagarajan P, Chung DW, Davie EW. Role of fibrinogen alpha and gamma chain sites in platelet aggregation. Proc Natl Acad Sci USA 1992; 89: 10729-10732.
176. Suehiro K, Gailit J, Plow EF. Fibrinogen is a ligand for integrin alpha5beta1 on endothelial cells. J Biol Chem 1997; 272: 5360-5366.
177. Yokoyama K, Zhang XP, Medved L, Takada Y. Specific binding of integrin alpha v beta 3 to the fibrinogen gamma and alpha E chain C-terminal domains. Biochemistry 1999; 38: 5872-5877.
178. Bach TL, Barsigian C, Yaen CH, Martinez J. Endothelial cell VEcadherin functions as a receptor for the beta15-42 sequence of fibrin. J Biol Chem 1998; 273: 30719-30728.
179. Gorlatov S, Medved L. Interaction of fibrin(ogen) with the endothelial cell receptor VE-cadherin: mapping of the receptor-binding site in the NH2-terminal portions of the fibrin beta chains. Biochemistry 2002; 41: 4107-4116.
180. Petzelbauer P, Zacharowski PA, Miyazaki Y, et al. The fibrinderived peptide Bbeta15-42 protects the myocardium against ischemia-reperfusion injury. Nat Med 2005; 11: 298-304.
181. Busso N, Peclat V, Van Ness K, et al. Exacerbation of antigeninduced arthritis in urokinase-deficient mice. J Clin Invest 1998; 102: 41-50.
182. Masson-Bessiere C, Sebbag M, Girbal-Neuhauser E, et al. The major synovial targets of the rheumatoid arthritis-specific antifilaggrin autoantibodies are deiminated forms of the alpha- and betachains of fibrin. J Immunol 2001; 166: 4177-4184.
183. So AK, Varisco PA, Kemkes-Matthes B, et al. Arthritis is linked to local and systemic activation of coagulation and fibrinolysis pathways. J Thromb Haemost 2003; 1: 2510-2515.
184. Jin T, Tarkowski A, Carmeliet P, Bokarewa M. Urokinase, a constitutive component of the inflamed synovial fluid, induces arthritis. Arthritis Res Ther 2003; 5: R9-R17.
185. Busso N, Peclat V, So A, Sappino AP. Plasminogen activation in synovial tissues: differences between normal, osteoarthritis, and rheumatoid arthritis joints. Ann Rheum Dis 1997; 56: 550-557.
186. Guiducci S, Del Rosso A, Cinelli M, et al. Rheumatoid synovial fibroblasts constitutively express the fibrinolytic pattern of invasive tumor-like cells. Clin Exp Rheumatol 2005; 23: 364-372.