Skip to main content
SpringerLink
Log in

Importance of Metalloproteinases and Macrophages in Viper Snake Envenomation–Induced Local Inflammation

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

The inflammatory action of jararhagin, a hemorrhagic metalloproteinase from Bothrops jararaca venom, was studied in mice using dorsal air pouches. The injection of the toxin in 6-day-old air pouches resulted in a leukocyte accumulation comparable to that induced by LPS and whole venom. Polymorphonuclear and mononuclear cells were present in this infiltrate, with a predominance of neutrophils. Treatment of jararhagin with 1,10-phenantroline abolished its proteolytic activity and reduced the pro-inflammatory effect in approximately 50%. Cell influx was not observed when jararhagin was injected into 1-hr air pouches devoid of macrophages, except when it was injected together with 106 syngeneic peritoneal macrophages. Supernatants of macrophages stimulated in vitro with jararhagin did not induce leukocyte influx in 1-hr air pouches; the influx occurred after injection of the pellets of stimulated cultures. In summary, jararhagin is an important pro-inflammatory component of B. jararaca venom, and its activity is dependent upon the proteolytic activity and the presence of macrophages.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Rosenfeld, G. 1971. Symptomatology, pathology and treatment of snake bites in South America. Venomous animals and their venoms. Vol. 2, pp. 345–362 (W. Bucherl and E. E. Buckley, eds.). New York: Academic Press.

    Google Scholar 

  2. Farsky, S. H. P., J. W. M. Costa-Cruz, Y. Cury, and C. F. P. Teixeira. 1997. Leukocyte response induced by Bothrops jararaca venom: In vivo and in vitro studies. Toxicon 35:185–193.

    Google Scholar 

  3. Trebien, H. A. and J. B. Calixto. 1989 Pharmological evaluation of rat paw edema induced by bothrops jararaca venom. Agent Action 26: 292-300.

    Google Scholar 

  4. teixeira, C. F. P., Y. Cury, and S. N. Jancar. 1994. hyperalgesia induced by bothrops jararaca venom in rats: Role of eicosanoids and platelet activating factor (PAF). toxicon. 32 419-424.

    Google Scholar 

  5. Paine, M. J. I., H. P. Desmond, R. D. G. Theakston, and J. M. Crampton. 1992. Purification, cloning, and molecular characterization of a high molecular weight hemorrhagic metalloproteinase, jararhagin, from Bothrops jararaca venom. J. Biol. Chem. 267:22869–22876.

    Google Scholar 

  6. Matsui, T., Y. Fujimura, and K. Titani. 2000. Snake venom proteases affecting hemostasis and thrombosis. Biochimica et Biophysica Acta 1477:146–156.

    Google Scholar 

  7. Kamiguti, A. S., C. R. M. Hay, R. D. G. Theakston, and M. Zuzel. 1996. Insights into the mechanism of haemorrhage caused by snake venom metalloproteinases. Toxicon. 34:627–642.

    Google Scholar 

  8. Moura-da-Silva, A. M., C. Marcinkiewicz, M. Marcinkiewicz, and S. Niewiarowski. 2001. Selective recognition of α2α1 integrin by jararhagin, a metalloproteinase ?disintegrin from Bothrops jararaca venom. Thromb. Res. 102:153–159.

    Google Scholar 

  9. Blobel, C. P. 1997. Metalloprotease-disintegrins: Links to cell adhesion and cleavage of TNF alpha and Notch. Cell 90:589–592.

    Google Scholar 

  10. Black, R. A., C. T. Rauch, C. J. Kozlosky, J. J. Peschon, J. L. Slack, M. F. Wolfson, B. J. Castner, K. L. Stocking, P. Reddy, S. Srinivasan, N. Nelson, N. Boiani, K. A. Schooley, M. hart, R. Davis, J. N. Fitzner, R. S. Johnson, R. J. Paxton, C. J. March, and D. P. Cerreti. 1997. A metalloproteinase disintegrin that releases tumour-necrosis factor-a from cells. Nature 385:729–733.

    Google Scholar 

  11. Moura-da-Silva, A. M., G. D. Laing, M. J. I. Paine, J. M. T. J. Dennison, V. Politi, J. M. Crampton, and R. D. G. Theakston. 1996. Processing of pro-tumor necrosis factor-a by venom metalloproteinases: A hypothesis explaining local tissue damage following snake bite. Eur. J. Immunol. 26:2000–2005.

    Google Scholar 

  12. Ahluwalia, A. and M. Perreti. 1996. Involvement of bradikinin b1 receptors in the polymorphonuclear leukocyte accumulation induced by IL-1b in vivo in the mouse. J. Immunol. 156:269–274.

    Google Scholar 

  13. Rucavado, A., J. Nunez, and J. M. Gutierrez. 1998. Blister formation and skin damage induced by BaP1, a hemorrhagic metalloproteinase from the venom of the snake Bothrops asper. Int. J. Exp. Pathol. 79:245–254.

    Google Scholar 

  14. Clissa, P. B., G. D. Laing, R. D. G. Theakston, I. Mota, M. J. Taylor, and A. M. Moura-da-Silva. 2001. The effect of jararhagin, a metalloproteinase isolated from Bothrops jararaca snake venom, on pro-inflammatory cytokines released by peritoneal adherent cells. Toxicon. 39:1567–1573.

    Google Scholar 

  15. Hogaboam, C. M., M. L. Steinhauser, S. W. Chensue, and S. L. Kunkel. 1998. Novel roles for chemokines and fibroblasts in interstitial fibrosis. Kidney Int. 54:2152–2159.

    Google Scholar 

  16. Dayer, J. M., S. Ricard-Blum, M. T. Kaufmann, and D. Herbage. 1986. Type IX collagen is a potent inducer of PGE2 and interleukin-1 production by human monocyte macrophages. FEBS Lett. 198:208–212.

    Google Scholar 

  17. Sedgwick, A. D., Y. M. Sin, J. C. W. Edwards, and D. A. Willaoughby. 1983. Increased inflammatory reactivity in newly formed lining tissue. J. Pathol. 141:483–495.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratório de Imunopatologia, Instituto Butantan, São Paulo, Brazil

    E. P. Costa, P. B. Clissa & A. M. Moura-da-Silva

  2. Laboratório de Farmacologia, Instituto Butantan, São Paulo, Brazil

    C. F. P. Teixeira

Authors
  1. E. P. Costa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. B. Clissa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. F. P. Teixeira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. M. Moura-da-Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Costa, E.P., Clissa, P.B., Teixeira, C.F.P. et al. Importance of Metalloproteinases and Macrophages in Viper Snake Envenomation–Induced Local Inflammation. Inflammation 26, 13–17 (2002). https://doi.org/10.1023/A:1014465611487

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1014465611487

Search

Navigation