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A relevant enzyme in granulomatous reaction, active matrix metalloproteinase-9, found in bovine Echinococcus granulosus hydatid cyst wall and fluid

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Abstract

In addition to the ability of matrix metalloproteinases (MMP) to degrade components of the extracellular matrix and their involvement in pathology-related processes of tissue remodeling, they were recently reported to enhance inflammation by activation of proinflammatory cytokines, or their release from the cell surface. In the work reported here, proteolytic activity previously found for hydatid cysts was further characterized as MMP-9. Active host MMP-9 was found in walls and fluids of bovine hydatid cysts of Echinococcus granulosus in the environment of granulomatous reaction. Pooled walls and fluids of hydatid cysts obtained from infected cattle were processed. Strong proteolytic activity was detected by zymography. The proteolytic fraction was purified by anion exchange and gelatin-agarose affinity chromatography. Major proteinases of the purified fraction were subjected to mass spectrometry and their identities were further confirmed by Western blotting using commercial anti-human MMP-9 monoclonal antibodies. Two proteinases were characterized as latent and active forms of host MMP-9. Using the same antibody for immunoblot, activity was localized, in paraffin-embedded sections of the parasite and the local host environment, to epithelioid and giant multinucleated cells. It is proposed here that MMP-9 is secreted by specialized host cells of monocytic lineage (epithelioid/giant cells) as an effector, in an attempt to digest the persistent foreign body. In vivo activation of MMP-9 suggests its involvement in inflammatory reaction and in the chemotaxis of inflammatory cells to the cyst. However, E. granulosus can deal efficiently with MMP-9. Research is suggested into possible immune evasion mechanisms, including the secretion of an inhibitory molecule.

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References

  • Bjorklund M, Koivunen E (2005) Gelatinase-mediated migration and invasion of cancer cells. Biochim Biophys Acta 1755:37–69

    PubMed  Google Scholar 

  • Coltorti EA, Varela-Díaz VM (1972) IgG levels and host specificity in hydatid cyst fluid. J Parasitol 58:753

    Article  PubMed  CAS  Google Scholar 

  • Coltorti EA, Varela-Díaz VM (1974) Echinococcus granulosus: penetration of macromolecules and their localization on the parasite membranes of cysts. Exp Parasitol 35:225–231

    Article  Google Scholar 

  • Chordi A, Kagan IG (1965) Identification and characterization of antigenic components of sheep hydatid fluid by immunoelectrophoresis. J Parasitol 51:63

    Article  PubMed  CAS  Google Scholar 

  • Craig PS (1988) Immunology of human hydatid disease. In: Grimwade AM (ed) ISI atlas of science: immunology. Institute for Scientific Information, Philadelphia, p 95

    Google Scholar 

  • Díaz A, Ferreira AM, Sim RB (1997) Complement evasion by Echinococcusgranulosus: sequestration of host factor H in the hydatid cyst wall. J Immunol 158:3779–3786

    PubMed  Google Scholar 

  • Díaz A, Ibarguren S, Breijo M, Willis A, Sim R (2000a) Host-derived annexin II at the host–parasite interface of the Echinococcus granulosus hydatid cyst. Mol Biochem Parasitol 110:171–176

    Article  PubMed  Google Scholar 

  • Díaz A, Willis A, Sim R (2000b) Expression of the proteinase specialized in bone resorption, cathepsin K, in granulomatous inflammation. Mol Med 6(8):648–659

    PubMed  Google Scholar 

  • Eckert J, Deplazes P (2004) Biological, epidemiological, and clinical aspects of Echinococcosis a zoonosis of increasing concern. Clin Microbiol Rev 17(1):107–135 (Jan)

    Article  PubMed  Google Scholar 

  • Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev 2:161–174

    CAS  Google Scholar 

  • Fernández C (1992) Studies on the glutathione S-transferase(s) from Echinococcus granulosus protoscoleces. Doctoral dissertation, University of Cambridge, Cambridge, UK

    Google Scholar 

  • Fridman R, Toth M, Pena D, Mobashery S (1995) Activation of progelatinase B (MMP-9) by gelatinase A (MMP-2). Cancer Res 55:2548–2555

    PubMed  CAS  Google Scholar 

  • Fridman R, Toth M, Chvyrkova I, Meroush O, Mobashery S (2003) Cell surface association of matrix metalloproteinase-9 (gelatinase B). Cancer Metastasis Rev 22:153–166

    Article  PubMed  CAS  Google Scholar 

  • Gómez D, De Lorenzo M, Alonso D, Andrade Z (1999) Expression of metalloproteinases (MMP-1, MMP-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2) in schistosomal portal fibrosis. Am J Trop Med Hyg 61(1):9–13 (Jul)

    PubMed  Google Scholar 

  • Heath DD (1995) Immunology and Echinococcus infections. In: Thompson RCA, Lymberly AJ (eds) Echinococcus and hydatid disease. CAB International, Wallingford, UK, p 183

    Google Scholar 

  • Izzo A, Izzo L, Kasimos J, Majka S (2004) A matrix metalloproteinase inhibitor promotes granuloma formation during early phase of Mycobacterium tuberculosis pulmonary infection. Tuberculosis 84:387–396

    Article  PubMed  CAS  Google Scholar 

  • Kagan IG, Norman L (1963) The isolation and characterization of two host antigens in hydatid cyst fluid of Echinococcus granulosus. Am J Trop Med Hyg 12:346

    PubMed  CAS  Google Scholar 

  • Kovaleva ES, Masler EP, Skantar AM, Chitwood DJ (2004) Novel matrix metalloproteinase from the cyst nematodes Heterodera glycines and Globodera rostochiensis. Mol Biochem Parasitol 136(1):109–112 (Jul)

    Article  PubMed  CAS  Google Scholar 

  • Lightowlers MW (1990) Immunology and molecular biology of Echinococcus infections. Int J Parasitol 20:471

    Article  PubMed  CAS  Google Scholar 

  • Lightowlers MW, Gottstein B (1995) Echinococcosis/hydatidosis: antigens, immunological and molecular diagnosis. In: Thompson RCA, Lymbery AJ (eds) Echinococcus and hydatid disease. CAB International, Wallingford UK, pp 355–410

    Google Scholar 

  • Marco M, Nieto A (1991) Metalloproteinases in the larvae of Echinococcus granulosus. Int J Parasitol 21(6):743–746

    Article  PubMed  CAS  Google Scholar 

  • Matthews BE (1982) Behaviour and enzyme release by Anisakis sp larvae (Nematoda: Ascaridida). J Helminthol 56:177–183

    Article  PubMed  CAS  Google Scholar 

  • McCawley LJ, Matrisian LM (2001) Matrix metalloproteinases: they’re not just for matrix anymore! Curr Opin Cell Biol 13:534–540

    Article  PubMed  CAS  Google Scholar 

  • McKerrow (1989) Parasite proteases. Exp Parasitol 68:111–115

    Article  PubMed  CAS  Google Scholar 

  • McKerrow JH, Doenhoff MJ (1988) Schistosoma proteases. Parasitol Today 12:334–449

    Article  Google Scholar 

  • McKerrow JH, Brindley P, Brown M, Gam AA, Stunton C, Neva FA (1990) Strongyloides stercoralis: identification of a protease that facilitates penetration of skin by the infective larvae. Exp Parasitol 70:134–143

    Article  PubMed  CAS  Google Scholar 

  • Morris SR, Sakanari JA (1994) Characterization of the serine protease and serine protease inhibitor from the tissue-penetrating nematode Anisakis simplex. J Biol Chem 269:27650–27656

    PubMed  CAS  Google Scholar 

  • Nagase H (1997) Activation mechanisms of matrix metalloproteinases. Biol Chem 378(3–4):151–160 (Mar)

    PubMed  CAS  Google Scholar 

  • Nagase H, Woesner JF (1999) Matrix metalloproteinases. J Biol Chem 274:21491–21494

    Article  PubMed  CAS  Google Scholar 

  • Okada Y, Gonoji Y, Naka K, Tomita K, Nakanishi I, Iwata K, Yamashita K, Hayakawa T (1992) Matrix metalloproteinase 9 (92-kDa gelatinase/type IV collagenase) from HT 1080 human fibrosarcoma cells. Purification and activation of the precursor and enzymic properties. J Biol Chem 267(30):21712–21719 (Oct 25)

    PubMed  CAS  Google Scholar 

  • Opdenakker G, Van den Steen P, Van Damme J (2001) Gelatinase B: a tuner and amplifier of immune functions. Trends Immunol 22(10):571–579 (Oct)

    Article  PubMed  CAS  Google Scholar 

  • Opdenakker G, Nelissen I, Van Damme J (2003) Functional roles and therapeutic targeting of gelatinase B and chemokines in multiple sclerosis. Lancet Neurol 2:747–756 (Dec)

    Article  PubMed  CAS  Google Scholar 

  • Parks W, Wilson C, Lopez-Boado Y (2004) Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol 4:617–629 (Aug)

    Article  PubMed  CAS  Google Scholar 

  • Petralanda I, Yarzabal L, Piessens WF (1986) Studies on a filarial antigen with collagenase activity. Mol Biochem Parasitol 19:51–59

    Article  PubMed  CAS  Google Scholar 

  • Quiding-Jarbrink M, Smith D, Bancroft G (2001) Production of matrix metalloproteinases in response to mycobacterial infection. Infect Immun 69(9):5661–5670 (Sep)

    Article  PubMed  CAS  Google Scholar 

  • Rasheed S, Nelson-Rees W, Toth E, Arnstein P, Gardner M (1974) Characterization of a newly derived human sarcoma cell line (HT1080). Cancer 33:1027–1033

    Article  PubMed  CAS  Google Scholar 

  • Robertson BD, Bianco AT, Mc Kerrow JH, Maizels RM (1989) Toxocara canis: proteolytic enzymes secreted by the infective larvae in vitro. Exp Parasitol 69:30–36

    Article  PubMed  CAS  Google Scholar 

  • Shapiro SZ, Bahr GM, Hira PR (1992) Analysis of host components in hydatid cyst fluid and immunoblot diagnosis of human Echinococcus granulosus infection. Ann Trop Med Parasitol 86:503

    PubMed  CAS  Google Scholar 

  • Taggart C, Greene C, Carrol T, O’Neill S, McElvaney N (2005) Elastolytic proteases, inflammation resolution and deregulation in chronic infective lung disease. Am J Respir Crit Care Med 171:1070–1076

    Article  PubMed  Google Scholar 

  • Thomas J, Kothare SN (1975) Tissue response in hydatidosis. Indian J Med Res 63(12):1761–1766 (Dec)

    PubMed  CAS  Google Scholar 

  • Thompson RCA (1995) Biology and systematics of Echinococcus. In: Thompson RCA, Lymbery AJ (eds) Echinococcus and hydatid disease. CAB International, Wallingford, UK, pp 1–50

    Google Scholar 

  • Towbin H, Stahelin T, Gordon J (1979) Electroforetic transfer of protein from polyacrylamide gels to nitrocellulose sheets. Proc Natl Acad Sci USA 76:4350

    Article  PubMed  CAS  Google Scholar 

  • Trancart MM, Chalmeigne N, Girardot C, Zarpanelian C, Prigent D (1992) Gelatinase is the main matrix metalloproteinase involved in granuloma-induced cartilage degradation. Int J Tissue React 14(6):287–294

    PubMed  CAS  Google Scholar 

  • Turk J (1989) Current status review: a comparison of secretory epithelioid cells and phagocytosing macrophages in experimental mycobacterial granulomas. Br J Path 70:589–596

    CAS  Google Scholar 

  • Uparanukraw P, Morakote N, Harnnoi T, Dantrakool A (2001) Molecular cloning of a gene encoding matrix metalloproteinase-like protein from Gnathostoma spinigerum. Parasitol Res 87:751–757

    Article  PubMed  CAS  Google Scholar 

  • Van den Steen P, Dubois B, Nelissen I, Rudd P, Dwek R, Opdenakker G (2002) Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9). Crit Rev Biochem Mol Biol 37(6):375–536

    Article  PubMed  Google Scholar 

  • Varela-Díaz VM, Coltorti EA (1972) Further evidence of the passage of host immunoglobulins into hydatid cysts. J Parasitol 58:1015–1016

    Article  PubMed  Google Scholar 

  • Varela-Díaz VM, Coltorti EA (1973) The presence of host immunoglobulins in hydatid cyst membranes. J Parasitol 59:484–488

    Article  PubMed  Google Scholar 

  • Wada K, Sato H, Kinoh H, Kajita M, Yamamoto H, Seiki M (1998) Cloning of three Caenorhabditis elegans genes potentially encoding novel matrix metalloproteinases. Gene 211:57–62

    Article  PubMed  CAS  Google Scholar 

  • Williams G, Williams W (1983) Granulomatous inflammation—a review. J Clin Pathol 36:723–733

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by SAREC, CONICYT, CSIC (University of Uruguay), and CEE. The text was revised by Eduardo Speranza.

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Authors and Affiliations

  1. Cátedra de Inmunología, Facultad de Química, Facultad de Ciencias, Instituto de Higiene, Universidad de la República, Av. Alfredo Navarro 3051, Segundo Piso, Montevideo, CP 11600, Uruguay

    M. Marco, A. Baz, C. Fernandez, G. Gonzalez, G. Salinas & A. Nieto

  2. Ludwig Institute for Cancer Research (Uppsala Branch), Uppsala, Sweden

    U. Hellman

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  1. M. Marco
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  2. A. Baz
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  3. C. Fernandez
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  4. G. Gonzalez
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  5. U. Hellman
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  6. G. Salinas
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  7. A. Nieto
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Correspondence to M. Marco.

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Marco, M., Baz, A., Fernandez, C. et al. A relevant enzyme in granulomatous reaction, active matrix metalloproteinase-9, found in bovine Echinococcus granulosus hydatid cyst wall and fluid. Parasitol Res 100, 131–139 (2006). https://doi.org/10.1007/s00436-006-0237-5

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  • DOI: https://doi.org/10.1007/s00436-006-0237-5

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