Tissue factor pathway inhibitor-2 (TFPI-2) recognizes the complement and kininogen binding protein gC1qR/p33 (gC1qR): implications for vascular inflammation

Ellinor I. B. Peerschke; Ramona J. Petrovan; Berhane Ghebrehiwet; Wolfram Ruf

doi:10.1160/TH04-03-0188

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 92(04): 811-819
DOI: 10.1160/TH04-03-0188

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Tissue factor pathway inhibitor-2 (TFPI-2) recognizes the complement and kininogen binding protein gC1qR/p33 (gC1qR): implications for vascular inflammation

Ellinor I. B. Peerschke

¹ Department of Pathology,Weill Medical College of Cornell University; New York, USA

,

Ramona J. Petrovan

² Department of Immunology,The Scripps Research Institute, La Jolla, California, USA

,

Berhane Ghebrehiwet

³ Department of Medicine, Stony Brook University, Stony Brook, New York, USA

,

Wolfram Ruf

² Department of Immunology,The Scripps Research Institute, La Jolla, California, USA

› Author Affiliations

Abstract

Summary

Evidence is accumulating to suggest that TFPI-2 is involved in regulating pericellular proteases implicated in a variety of physiologic and pathologic processes including cancer cell invasion, vascular inflammation, and atherosclerosis. Recent immunohistochemical studies of advanced atherosclerotic lesions, demonstrated a similar tissue distribution for TFPI-2, High Molecular Weight Kininogen (HK), and gC1qR/p33 (gC1qR), a ubiquitously expressed, multicompartmental cellular protein involved in modulating complement, coagulation, and kinin cascades. Further studies to evaluate TFPI-2 interactions with gC1qR demonstrated direct interactions between gC1qR and TFPI-2 using immunoprecipitation and solid phase binding studies. Specific and saturable binding between TFPI-2 and gC1qR (estimated Kd: ∼ 70 nM) was observed by ELISA and surface plasmon resonance (Biacore) binding assays. Binding was inhibited by antibodies to gC1qR, and was strongly dependent on the Kunitz-2 domain of TFPI-2, as deletion of this domain reduced gC1qR-TFPI-2 interactions by approximately 75%. Deletion of gC1qR amino acids 74-95, involved in C1q binding, had no effect on gC1qR binding to TFPI-2, although antibodies to this region and purified C1q both inhibited binding, most likely via allosteric effects. In contrast, HK did not affect TFPI-2 binding to gC1qR. Binding of TFPI-2 to gC1qR produced statistically significant but modest reductions in TFPI-2 inhibition of plasmin, but had no effect on kallikrein inhibition in fluid phase chromogenic assays. Taken together, these data suggest that gC1qR may participate in tissue remodeling and inflammation by localizing TFPI-2 to the pericellular environment to modulate local protease activity and regulate HK activation.

Keywords

Fibrinolysis inhibitors - proteases / inhibitors - proteolysis / pericellular - tissue factor pathway inhibitor (TFPI) - atherosclerosis

Full Text

References

References
1 Newby AC, Southgate KM, Davies M. Extracellular matrix degrading metalloproteinases in the pathogenesis of arteriosclerosis. Basic Res Cardiol 1994; 89 (Suppl) 59-70.
2 Nagase H, Woessner JH. Matrix metalloproteinases. J Biol Chem 1999; 274: 21491-4.
3 Curran S, Murray GI. Matrix metalloproteinases in tumour invasion and metastasis. J Pathol 1999; 189: 300-8.
4 Libby P, Lee RT. Matrix matters. Circulation 2000; 102: 1874-6.
5 Petersen LC, Sprecher CA, Foster DC. et al. Inhibitory properties of a novel human Kunitz-type protease inhibitor homologous to tissue factor pathway inhibitor. Biochemistry 1996; 35: 266-72.
6 Rao CN, Reddy P, Lie Y. et al. Extracellular matrix-associated serine protease inhibitors (Mr 33,000, 31,000, and 27,000) are single gene-products with differential glycosylation: cDNA cloning of the 33-kDa inhibitor reveals its identity to tissue factor pathway inhibitor-Arch Biochem Biophys. 1996; 335: 82-92.
7 Herman MP, Sukhova GK, Kisiel W. et al. Tissue factor pathway inhibitor-2 is a novel inhibitor of matrix metalloproteinases with implications for atherosclerosis. J Clin Invest 2001; 107: 1117-26.
8 Rice A, Chard T. A method for the purification of placental protein 5 (PP5) from placental extracts. Clin Chim Acta 1983; 131: 289-94.
9 Udagawa K, Miyagi Y, Hirahara F. et al. Specific expression of PP5/TFPI2 mRNA by syncytiotrophoblasts in human placenta as revealed by in situ hybridization. Placenta 1998; 19: 217-23.
10 Udagawa K, Yasumitsu H, Esaki M. et al. Subcellular localization of PP5 TFPI-2 in human placenta: possible role of PP5 TFPI-2 as an anticoagulant on the surface of syncytiotrophoblasts. Placenta 2002; 23: 145-53.
11 Iino M, Foster DC, Kisiel W. Quantification and characterization of human endothelial cell derived tissue factor pathway inhibitor-2. Arterioscler Thromb Vasc Biol 1994; 71: 275-9.
12 Miyagi Y, Koshikawa N, Yasumitsu H. et al. cDNA cloning and mRNA expression of a serine proteinase secreted by cancer cells: identification as placental protein 5 and tissue factor pathway inhibitor. J Biochem 1994; 116: 939-42.
13 Crawley JTB, Goulding DA, Ferreira V. et al. Expression and localization of tissue factor pathway inhibitor-2 in normal and atherosclerotic human vessels. Arterioscler Thromb Vasc Biol 2002; 22: 218-24.
14 Peerschke EIB, Minta JO, Zhou SZ. et al. Expression of gC1qR/p33 and its major ligands in human atherosclerotic lesions. Molec Immunol 2004; 41: 759-66.
15 Ghebrehiwet B, Lim BL, Peerschke EIB. et al. Isolation, cDNA cloning, and overexpression of a 33-kDa cell surface glycoprotein that binds to the globular ‘heads’ of C1q. J Exp Med 1994; 179: 1809-21.
16 Deb TB, Datta K. Molecular cloning of human fibroblast hyaluronic acid binding protein confirms its identity with P-32, a protein copurified with splicing factor SF2. J Biol Chem 1996; 269: 2206-12.
17 Ghebrehiwet B, Lim B-L, Kumar R. et al. gC1qR/p33: a member of a new class of multifunctional and multicompartmental cellular proteins is involved in inflammation and infection. Immunol Rev 2001; 180: 65-77.
18 Ghebrehiwet B, Jesty J, Peerschke EIB. gC1qR/p33: Structure-function predictions from the crystal structure. Immunobiology 2002; 205: 421-32.
19 Peerschke EIB, Ghebrehiwet B. Human blood platelet gC1qR. Immunol Rev 2001; 180: 56-64.
20 Joseph K, Ghebrehiwet B, Peerschke EIB. et al. Identification of the zinc-dependent endothelial cell binding protein for high molecular weight kininogen and factor XII: identity with the receptor which binds to the globular ‘heads’ of C1q (gC1q-R). Proc Natl Acad Sci USA 1996; 93: 8552-7.
21 Shibayama Y, Joseph K, Ghebrehiwet B. et al. Identification of gC1qR, the endothelial cell receptor for the globular heads of C1q as a naturally occurring initiator of the intrinsic blood coagulation and kinin-generating pathway. Blood 1996; 88: 524a.
22 Nguyen T, Ghebrehiwet B, Peerschke EIB. Staphylococcus aureus Protein A recognizes platelet gC1qR/p33: a novel mechanism for staphylococcus interactions with platelets. Infect Immun 2000; 68: 2061-8.
23 Braun L, Ghebrehiwet B, Cossart P. gC1qR/p33, a C1q binding protein, is a novel receptor for Listeria monocytogenes. EMBO J 2000; 19: 1458-66.
24 Kittlesen DJ, Chianese-Bullock KA, Yao ZQ. et al. Interaction between complement receptor gC1qR and hepatitis C virus core protein inhibits T-lymphocyte proliferation. J Clin Immunol 2000; 106: 1239-49.
25 Luo Y, Yu H, Peterlin PM. Cellular protein modulates effects of human immunodeficiency virus type 1 Tat transactivator and the general transcription factor TFPIIB with the cellular protein TAP. J Virol 1995; 69: 3017-23.
26 Rozanov DV, Ghebrehiwet B, Postnova TI. et al. The hemopexin-like C-terminal domain of membrane type matrix metalloproteinase regulates proteolysis of a multifunctional protein, gC1qR. J Biol Chem 2002; 277: 9318-25.
27 Fischer EG, Riewald M, Huang HY. et al. Tumor cell adhesion and migration supported by interaction of a receptor-protease complex with its inhibitor. J Clin Invest 1999; 104: 1213-21.
28 Ott I, Miyagi Y, Miyazaki K. et al. Reversible regulation of tissue factor-induced coagulation by glycosyl phosphatidylinositol-anchored tissue factor pathway inhibitor. Arterioscler Thromb Vasc Biol 2000; 20: 874-82.
29 Sprecher CA, Kisiel W, Mathews S. et al. Molecular cloning, expression, and partial characterization of a second human tissuefactor-pathway inhibitor. Proc Natl Acad Sci USA 1994; 91: 3353-7.
30 Wun TC, Kretzmer KK, Girard TJ. et al. Cloning and characterization of a cDNA coding for the lipoprotein-associated coagulation inhibitor shows that it consists of three tandem Kunitz-type inhibitory domains. J Biol Chem 1988; 263: 6001-4.
31 Stone MJ, Ruf W, Miles DJ. et al. Recombinant soluble human Tissue Factor secreted by Saccaromyces cerevisiae and refolded from Escherichia coli inclusion bodies: Glycosylation of mutants, activity, and physical characterization. Biochem J 1995; 310: 605-14.
32 Rao CN, Reddy P, Reeder DJ. et al. Prokaryotic expression, purification, and reconstitution of biological activities (antiprotease, antitumor, and heparin-binding) for tissue factor pathway inhibitor-2. Biochem Biophys Res Commun 2000; 276: 1286-94.
33 Ghebrehiwet B, Lu PD, Zhang W. et al. Identification of functional domains on gC1qR, a cell surface protein which binds to the globular “heads” of C1q, using monoclonal antibodies and synthetic peptides. Hybridoma 1996; 15: 333-42.
34 Menabawey M, Silman R, Rice A. et al. Dramatic increase of placental protein 5 levels following injection of small doses of heparin. Brit J Obstet Gynaecol 1985; 92: 207-10.
35 Sandset PM, Abildgaard U, Larsen ML. Heparin induces release of extrinsic coagulation pathway inhibitor (EPI). Thromb Res 1988; 50: 803-13.
36 Kario K, Matsuo T, Yamada T. et al. Increased tissue factor pathway inhibitor levels in uremic patients on regular hemodialysis. Thromb Haemost 1994; 71: 275-9.
37 Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680-5.
38 Guo WX, Ghebrehiwet B, Weksler B. et al. Upregulation of endothelial cell binding proteins/receptors for complement component C1q by inflammatory cytokines. J Lab Clin Med 1999; 133: 541-50.
39 Jiang J, Zhang Y, Krainer AR. et al. Crystal structure of p32, a doughnut-shaped acidic mitochondrial matrix protein. Proc Natl Acad Sci USA 1999; 96: 3572-7.
40 Blindt R, Vogt F, Lamby D. et al. Characterization of differential gene expression in quiescent and invasive human arterial smooth muscle cells. J Vasc Res 2002; 39: 340-52.
41 Jin M, Udagawa K, Miyagi E. et al. Expression of serine proteinase inhibitor PPGTFPI-2/MSPI decreases the invasive potential of human choriocarcinoma cells in vitro and in vivo. Gynecol Oncol 2001; 83: 325-33.
42 Konduri SD, Rao CN, Chandrasekar N. et al. A novel function of tissue factor pathway inhibitor-2 (TFPI-2) in human glioma invasion. Oncogene 2001; 20: 6938-45.
43 Konduri SD, Tasiou A, Chandrasekar N. et al. Role of tissue factor pathway inhibitor-2 (TFPI-2) in amelanotic melanoma (C-32) invasion. Clin Exp Metastasis 2000; 18: 303-8.
44 Neaud V, Hisaka T, Monvoisin A. et al. Paradoxical pro-invasive effect of the serine proteinase inhibitor tissue factor pathway inhibitor-2 on human hepatocellular carcinoma cells. J Biol Chem 2000; 275: 35565-9.
45 Mahdi F, Shariat-Madar Z, Todd III RF. et al. Expression and colocalization of cytokeratin I and urokinase plasminogen activator receptor on endothelial cells. Blood 2001; 97: 2342-50.
46 Peerschke EIB, Murphy TK, Ghebrehiwet B. Activation-dependent surface expression of gC1qR/p33 on human blood platelets. Thromb Haemost 2003; 89: 331-9.
47 Mahdi F, Madar ZS, Figueroa CD. et al. Factor XII interacts with the multiprotein assembly of urokinase plasminogen activator receptor, gC1qR, and cytokeratin 1 on endothelial cell membranes. Blood 2002; 99: 3585-96.
48 Chen A, Gaddipati S, Hong Y. et al. Human T cells express specific binding sites for C1q Role in T cell activation and proliferation. J Immunol 1994; 153: 1430-40.
49 Chad HS, Schmidt AE, Bajaj SP. et al. Structure-function analysis of the reactive site in the first Kunitz-type domain of human tissue factor pathway inhibitor-2. J Biol Chem 2004; 279: 17500-7.