Effects of a snake venom metalloproteinase, triflamp, on platelet aggregation, platelet-neutrophil and neutrophilneutrophil interactions: involvement of platelet GPIbα. and neutrophil PSGL-1

Yu-Lun Tseng; Chia-Jung Lee; Tur-Fu Huang

doi:10.1160/TH03-07-0426

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2004; 91(02): 315-324
DOI: 10.1160/TH03-07-0426

Platelets and Blood Cells

Schattauer GmbH

Effects of a snake venom metalloproteinase, triflamp, on platelet aggregation, platelet-neutrophil and neutrophilneutrophil interactions: involvement of platelet GPIbα. and neutrophil PSGL-1

Authors

Yu-Lun Tseng

¹Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan
Chia-Jung Lee

¹Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan
Tur-Fu Huang

¹Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan

Abstract

Summary

The biologically active components fromViperidae venoms specifically affect cell-matrix interactions, and have been utilized for developing anti-adhesive therapy as anti-thrombotic and antiangiogenic agents. Utilizing platelet aggregometry coupled with flow cytometry, we found that a metalloproteinase isolated from Trimeresurus flavoviridis, termed triflamp, inhibited heterotypic adhesion between platelets and neutrophils in whole blood samples. Triflamp is a monomeric glycoprotein with a molecular weight of ∼28 kDa. Triflamp has a N-terminal amino acid sequence homologous to other venom metalloproteinases isolated from T. flavoviridis. The enzymatic activity of triflamp was inhibited by EDTA and phenanthroline but not by PMSF. Moreover, triflamp is a pure α-fibrinogenase. Studies aimed at determining the nature of triflamp in affecting platelets or neutrophils revealed a selective inhibitory activity to glycoprotein (GP) Ibα.-dependent platelet aggregation and PSGL-1-dependent neutrophil homotypic aggregation, indicating that its effects are rather specific. As judged by Western blotting, GPIbα. on platelets and PSGL-1 on neutrophils are the substrates of triflamp. In conclusion, we suggest the novel role of venom metalloproteinase from Viperidae affecting the blood cell-cell interactions, thus offering a potential approach for further exploration of anti-inflammatory agents.

Keywords

Triflamp - metalloproteinase - glycoprotein Ibα - PSGL-1 - neutrophil-platelet interaction

Full Text

References

References
1 McEver RP. Adhesive interactions of leukocytes, platelets, and the vessel wall during hemostasis and inflammation. Thromb Haemost 2001; 86: 746-56.
2 Evangelista V, Manarini S, Sideri R. et al. Platelet/polymorphonuclear leukocyte interaction: P-selectin triggers protein-tyrosine phosphorylation-dependent CD11b/CD18 adhesion: role of PSGL-1 as a signaling molecule. Blood 1999; 93: 876-85.
3 Nagata K, Tsuji T, Todoroki N. et al. Activated platelets induce superoxide anion release by monocytes and neutrophils through P-selectin (CD62). J Immunol 1993; 151: 3267-73.
4 Renesto P, Chignard M. Enhancement of cathepsin G-induced platelet activation by leukocyte elastase: consequence for the neutrophil-mediated platelet activation. Blood 1993; 82: 139-44.
5 Valles J, Santos MT, Marcus AJ. et al. Downregulation of human platelet reactivity by neutrophils. Participation of lipoxygenase derivatives and adhesive proteins. J Clin Invest 1993; 92: 1357-65.
6 Palabrica T, Lobb R, Furie BC. et al. Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets. Nature 1992; 359: 848-51.
7 Rinder CS, Bonan JL, Rinder HM. et al. Cardiopulmonary bypass induces leukocyteplatelet adhesion. Blood 1992; 79: 1201-5.
8 Bonomini M, Stuard S, Carreno MP. et al. Neutrophil reactive oxygen species production during hemodialysis: role of activated platelet adhesion to neutrophils through P-selectin. Nephron 1997; 75: 402-11.
9 Kupatt C, Habazettl H, Hanusch P. et al. c7E3Fab reduces postischemic leukocytethrombocyte interaction mediated by fibrinogen. Implications for myocardial reperfusion injury. Arterioscler Thromb Vasc Biol 2000; 20: 2226-32.
10 Serrano Jr CV, Ramires JA, Venturinelli M. et al. Coronary angioplasty results in leukocyte and platelet activation with adhesion molecule expression. Evidence of inflammatory responses in coronary angioplasty. J Am Coll Cardiol 1997; 29: 1276-83.
11 Huang TF. What have snakes taught us about integrins?. Cell Mol Life Sci 1998; 54: 527-40.
12 Lee LW, Peng HC, Ko WC. et al. Triflavin potentiates the antiplatelet activity of platelet activating factor receptor antagonist on activated neutrophil-induced platelet aggregation. Eur J Pharmacol 1999; 364: 239-46.
13 Konstantopoulos K, Neelamegham S, Burns AR. et al. Venous levels of shear support neutrophil-platelet adhesion and neutrophil aggregation in blood via P-selectin and β₂-integrin. Circulation 1998; 98: 873-82.
14 Kinsella JL, Ralph LJ, Ryan MF. A preliminary analysis of proteolytic activity of excretory-secretory products from Cyathostominea. Vet Parasitol 2002; 107: 73-83.
15 Languino LR, Plescia J, Duperray A. et al. Fibrinogen mediates leukocyte adhesion to vascular endothelium through an ICAM-1-dependent pathway. Cell 1993; 73: 1423-34.
16 Liu CZ, Hur BT, Huang TF. Measurement of glycoprotein IIb/IIIa blockade by flow cytometry with fluorescein isothiocyanate-conjugated crotavirin, a member of disintegrins. Thromb Haemost 1996; 76: 585-91.
17 Taylor AD, Neelamegham S, Hellums JD. et al. Molecular dynamics of the transition from L-selectin-to β₂-integrin-dependent neutrophil adhesion under defined hydrodynamic shear. Biophys J 1996; 71: 3488-500.
18 Clemetson KJ, Clemetson JM. Platelet collagen receptors. Thromb Haemost 2001; 86: 189-97.
19 Simon DI, Chen Z, Xu H. et al. Platelet glycoprotein Ibα is a counterreceptor for the leukocyte integrin Mac-1 (CD11b/CD18). J Exp Med 2000; 192: 193-204.
20 Miyata T, Takeya H, Ozeki Y. et al. Primary structure of hemorrhagic protein, HR2a, isolated from the venom of Trimeresurus flavoviridis . J Biochem 1989; 105: 847-53.
21 Iha M, Qi ZQ, Kannki T. et al. The primary structure of a hemorrhagic factor, HR2b, from the venom of Okinawa habu (Trimeresurus flavoviridis). Toxicon 1995; 33: 229-39.
22 Takeya H, Arakawa M, Miyata T. et al. Primary structure of H₂-proteinase, a nonhemorrhagic metalloproteinase, isolated from the venom of the Habu snake, Trimeresurus flavoviridis . J Biochem 1989; 106: 151-7.
23 Kishimoto M, Takahashi T. Molecular cloning and sequence analysis of cDNA encoding flavoridin, a disintegrin from the venom of Trimeresurus flavoviridis. . Toxicon 2002; 40: 1033-40.
24 Kornalik F. The influence of snake venom proteins on blood coagulation. In: Snake Toxins. Pergamon Press; 1991: 323-83.
25 Greco NJ, Jamieson GA. High and moderate affinity pathways for thrombin-induced platelet activation. Proc Soc Exp Biol Med 1991; 198: 792-9.
26 Snapp KR, Ding H, Atkins K. et al. A novel Pselectin glycoprotein ligand-1 monoclonal antibody recognizes an epitope within the tyrosine sulfate motif of human PSGL-1 and blocks recognition of both P- and L-selectin. Blood 1998; 91: 154-64.
27 De Luca M, Dunlop LC, Andrews RK. et al. A novel cobra venom metalloproteinase, mocarhagin, cleaves a 10-amino acid peptide from the mature N terminus of P-selectin glycoprotein ligand receptor, PSGL-1, and abolishes P-selectin binding. J Biol Chem 1995; 270: 26734-7.
28 Ward CM, Andrews RK, Smith AI. et al. Mocarhagin, a novel cobra venom metalloproteinase, cleaves the platelet von Willebrand factor receptor glycoprotein Ibα. Identification of the sulfated tyrosine/anionic sequence Tyr-276-Glu-282 of glycoprotein Ibα as a binding site for von Willebrand factor and alpha-thrombin. Biochemistry 1996; 35: 4929-38.
29 Matsui T, Fujimura Y, Titani K. Snake venom proteases affecting hemostasis and thrombosis. Biochim Biophys Acta 2000; 1477: 146-56.
30 Braud S, Bon C, Wisner A. Snake venom proteins acting on hemostasis. Biochimie 2000; 82: 851-9.
31 Gutierrez JM, Rucavado A. Snake venom metalloproteinases: their role in the pathogenesis of local tissue damage. Biochimie 2000; 82: 841-50.
32 Wu WB, Peng HC, Huang TF. Crotalin, a vWF and GP Ib cleaving metalloproteinase from venom of Crotalus atrox. Thromb Haemost 2001; 86: 1501-11.
33 Huang TF, Chang MC, Teng CM. Antiplatelet protease, kistomin, selectively cleaves human platelet glycoprotein Ib. Biochim Biophys Acta 1993; 1158: 293-9.
34 Bee A, Theakston RD, Harrison RA. et al. Novel in vitro assays for assessing the haemorrhagic activity of snake venoms and for demonstration of venom metalloproteinase inhibitors. Toxicon 2001; 39: 1429-34.
35 Smith CW. Possible steps involved in the transition to stationary adhesion of rolling neutrophils: a brief review. Microcirculation 2000; 07: 385-94.
36 Spangenberg P, Redlich H, Bergmann I. et al. The platelet glycoprotein IIb/IIIa complex is involved in the adhesion of activated platelets to leukocytes. Thromb Haemost 1993; 70: 514-21.
37 Ostrovsky L, King AJ, Bond S. et al. A juxtacrine mechanism for neutrophil adhesion on platelets involves platelet-activating factor and a selectin-dependent activation process. Blood 1998; 91: 3028-36.
38 Taniuchi Y, Kawasaki T, Fujimura Y. et al. Flavocetin-A and -B, two high molecular mass glycoprotein Ib binding proteins with high affinity purified from Trimeresurus flavoviridis venom, inhibit platelet aggregation at high shear stress. Biochim Biophys Acta 1995; 1244: 331-8.
39 Li R, Xie J, Kantor C. et al. A peptide derived from the intercellular adhesion molecule-2 regulates the avidity of the leukocyte integrins CD11b/CD18 and CD11c/CD18. J Cell Biol 1995; 129: 1143-53.
40 Anai K, Sugiki M, Yoshida E. et al. Inhibition of a snake venom hemorrhagic metalloproteinase by human and rat α-macroglobulins. Toxicon 1998; 36: 1127-39.
41 Svoboda P, Meier J, Freyvogel TA. Purification and characterization of three α₂-antiplasmin and α₂-macroglobulin inactivating enzymes from the venom of the Mexican west coast rattlesnake (Crotalus basiliscus). Toxicon 1995; 33: 1331-46.