Hostname: page-component-78c5997874-8bhkd Total loading time: 0 Render date: 2024-11-10T14:56:43.348Z Has data issue: false hasContentIssue false

Pharmacological action of tick saliva upon haemostasis and the neutralization ability of sera from repeatedly infested hosts

Published online by Cambridge University Press:  23 July 2009

J. RECK Jr.
Affiliation:
Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre - RS - Brazil
M. BERGER
Affiliation:
Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre - RS - Brazil
F. S. MARKS
Affiliation:
Departamento de Patologia Clínica Veterinária, Faculdade de Veterinária, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre - RS - Brazil
R. B. ZINGALI
Affiliation:
Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro - RJ - Brazil
C. W. CANAL
Affiliation:
Departamento de Patologia Clínica Veterinária, Faculdade de Veterinária, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre - RS - Brazil
C. A. S. FERREIRA
Affiliation:
Departamento de Biologia Celular e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre - RS - Brazil
J. A. GUIMARÃES
Affiliation:
Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre - RS - Brazil
C. TERMIGNONI*
Affiliation:
Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre - RS - Brazil Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre - RS - Brazil
*
*Corresponding author: Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves, 9500, P.O. Box 15005, ZIP Code 91501-970, Porto Alegre, RS, Brazil. Tel: +55 51 33086082. Fax +55 51 33087309. E-mail: ctermignoni@cbiot.ufrgs.br.

Summary

Ticks are blood-feeding arthropods widely distributed in the world and vectors of several diseases. As haematophagy demands evasion strategies and repeatedly infested hosts develop protective immune responses, we investigated the mechanisms of the Rhipicephalus (Boophilus) microplus saliva anti-haemostatic activity and the possible relationship between the acquired natural anti-tick host resistance and anti-haemostatic action. For this purpose, we studied the effects of R. microplus saliva on different pathways of haemostasis and tested whether repeated infested bovine sera (RIBS) are able to abolish salivary anti-haemostatic activities. R. microplus saliva (i) displays inhibitory activity upon collagen-induced platelet aggregation; (ii) inhibits the induction of endothelial pro-coagulant state; and (iii) reduces thrombogenesis in vivo. RIBS were shown to be able to partially block the delay of coagulation and the anti-thrombotic effect of saliva, and to totally abolish the modulation of endothelium activation. Conversely, RIBS has no effect on the inhibition of platelet aggregation. These results show, for the first time, the neutralization ability of sera from acquired resistance hosts against tick anti-haemostatics. Moreover, this is the first report of a haematophagous parasite able to modulate endothelial cell pro-coagulant state, and addresses the presence of anti-platelet and anti-thrombotic activity in R. microplus saliva.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Allen, J. R. (1994). Host resistance to ectoparasites. Revue Scientifique et Technique – Office International des Epizooties 13, 12871303.CrossRefGoogle ScholarPubMed
Berger, M., Pinto, A. F. and Guimarães, J. A. (2008). Purification and functional characterization of bothrojaractivase, a prothrombin-activating metalloproteinase isolated from Bothrops jararaca snake venom. Toxicon 51, 488501.CrossRefGoogle ScholarPubMed
Bohrer, C. B., Reck, J. J., Fernandes, D., Sordi, R., Guimarães, J. A., Assreuy, J. and Termignoni, C. (2007). Kallikrein kinin system activation by Lonomia obliqua caterpillar bristles: Involvement in edema and hypotension responses to envenomation. Toxicon 49, 663669.CrossRefGoogle ScholarPubMed
Born, G. V. R. and Cross, M. J. (1963). The aggregation of blood platelets. Journal of Physiology 168, 178195.CrossRefGoogle ScholarPubMed
Brossard, M. and Wikel, S. K. (2004). Tick immunobiology. Parasitology 129 (Suppl.), S161S176.CrossRefGoogle ScholarPubMed
Brown, R. E. (1989). Protein measurement using bicinchoninic acid: elimination of interfering substances. Analytical Biochemistry 180, 136139.CrossRefGoogle ScholarPubMed
Champagne, D. E. and Valenzuela, J. G. (1996). Pharmacology of haematophagous arthropod saliva. In The Immunology of Host-Ectoparasitic Arthropod Relationships (ed. Wikel, S. K.), pp. 85–106. CAB International, Wallingford, UK.Google Scholar
Ciprandi, A., Oliveira, S. K., Masuda, A., Horn, F. and Termignoni, C. (2006). Boophilus microplus: its saliva contains microphilin, a small thrombin inhibitor. Experimental Parasitology 114, 4046.CrossRefGoogle ScholarPubMed
Cruz, A. P., Silva, S. S., Mattos, R. T., Da Silva Vaz, I. Jr., Masuda, A. and Ferreira, C. A. (2008). Comparative IgG recognition of tick extracts by sera of experimentally infested bovines. Veterinary Parasitology 158, 152158.CrossRefGoogle ScholarPubMed
Déruaz, M., Frauenschuh, A., Alessandri, A. L., Dias, J. M., Coelho, F. M., Russo, R. C., Ferreira, B. R., Graham, G. J., Shaw, J. P., Wells, T. N., Teixeira, M. M., Power, C. A. and Proudfoot, A. E. (2008). Ticks produce highly selective chemokine binding proteins with anti-inflammatory activity. Journal of Experimental Medicine 205, 20192031.CrossRefGoogle Scholar
Dickinson, R. G., O'Hagan, J. E., Schotz, M., Binnington, K. C. and Hegarty, M. P. (1976). Prostaglandin in the saliva of the cattle tick Boophilus microplus. The Australian Journal of Experimental Biology and Medical Science 54, 475486.CrossRefGoogle ScholarPubMed
Edgell, C. J., McDonald, C. C. and Graham, J. B. (1983). Permanent cell line expressing human factor VIII-related antigen established by hybridization. Proceedings of the National Academy of Sciences, USA 80, 37343737.CrossRefGoogle ScholarPubMed
FASS. (1999). Guide for the Care and Use of Agricultural Animals in Agricultural Research and Teaching. 1st Edn., Federation of Animal Science Societies, Savoy, USA.Google Scholar
Ferreira, C. A., Da Silva Vaz, I., Silva, S. S., Haag, K. L., Valenzuela, J. G. and Masuda, A. (2002). Cloning and partial characterization of a Boophilus microplus (Acari: Ixodidae) calreticulin. Experimental Parasitology 101, 2534.CrossRefGoogle ScholarPubMed
Francischetti, I. M., Valenzuela, J. G., Andersen, J. F., Mather, T. N. and Ribeiro, J. M. (2002). Ixolaris, a novel recombinant tissue factor pathway inhibitor (TFPI) from the salivary gland of the tick, Ixodes scapularis: identification of factor X and factor Xa as scaffolds for the inhibition of factor VIIa/tissue factor complex. Blood 99, 36023612.CrossRefGoogle ScholarPubMed
Francischetti, I. M., Mather, T. N. and Ribeiro, J. M. (2004). Penthalaris, a novel recombinant five-Kunitz tissue factor pathway inhibitor (TFPI) from the salivary gland of the tick vector of Lyme disease, Ixodes scapularis. Thrombosis and Haemostasis 91, 886898.Google ScholarPubMed
Francischetti, I. M. B., Mather, T. N. and Ribeiro, J. M. C. (2005). Tick saliva is a potent inhibitor of endothelial cell proliferation and angiogenesis. Thrombosis and Haemostasis 94, 167174.Google ScholarPubMed
Francischetti, I. M., Sa-Nunes, A., Mans, B. J., Santos, I. M. and Ribeiro, J. M. (2009). The role of saliva in tick feeding. Frontiers in Bioscience 14, 20512088.CrossRefGoogle ScholarPubMed
Fioravanti, C., Burkholder, D., Francis, B., Siegl, P. K. and Gibson, R. E. (1993). Antithrombotic activity of recombinant tick anticoagulant peptide and heparin in a rabbit model of venous thrombosis. Thrombosis Research 71, 317324.CrossRefGoogle Scholar
Gibbons, G. H. (1998). The vascular response to injury. In Thrombosis and Hemorrhage (ed. Loscalzo, J. and Schafer, A. I.), pp. 307320, 2nd Edn. Williams & Wilkins, Baltimore, MD, USA.Google Scholar
Guimarães, J. H., Tucci, E. C. and Barros-Battesti, D. M. (2001). Ectoparasitos de Importância Veterinária. 1st Edn. Editora Plêiade, São Paulo, Brazil.Google Scholar
Horn, F., Santos, P. C. and Termignoni, C. (2000). Boophilus microplus anticoagulant protein: an antithrombin inhibitor isolated from the cattle tick saliva. Archives of Biochemistry and Biophysics 384, 6873.CrossRefGoogle ScholarPubMed
Jackson, L. A. and Opdebeeck, J. P. (1995). The effect of various adjuvants on the humoral immune response of sheep and cattle to soluble and membrane midgut antigens of Boophilus microplus. Veterinary Parasitology 58, 129141.CrossRefGoogle ScholarPubMed
Johnson, S., Sypura, W. D., Gerding, D. N., Ewing, S. L. and Janoff, E. N. (1995). Selective neutralization of a bacterial enterotoxin by serum immunoglobulin A in response to mucosal disease. Infection and Immunity 63, 31663173.CrossRefGoogle ScholarPubMed
Johnston, L. A., Kemp, D. H. and Pearson, R. D. (1986). Immunization of cattle against Boophilus microplus using extracts derived from adult female ticks: effects of induced immunity on tick populations. International Journal for Parasitology 16, 2734.CrossRefGoogle ScholarPubMed
Jongejan, F. and Uilenberg, G. (2004). The global importance of ticks. Parasitology 129 (Suppl.), S3–S14.CrossRefGoogle ScholarPubMed
Juncadella, I. J., Garg, R., Ananthnarayanan, S. K., Yengo, C. M. and Anguita, J. (2007). T-cell signaling pathways inhibited by the tick saliva immunosuppressor, Salp15. FEMS Immunology and Medical Microbiology 49, 433438.CrossRefGoogle ScholarPubMed
Kemp, D. H., Hales, J. R., Schleger, A. V. and Fawcett, A. A. (1983). Comparison of cutaneous hyperemia in cattle elicited by larvae of Boophilus microplus and by prostaglandins and other mediators. Experientia 39, 725727.CrossRefGoogle ScholarPubMed
Kimaro, E. E. and Opdebeeck, J. P. (1994). Tick infestations on cattle vaccinated with extracts from the eggs and the gut of Boophilus microplus. Veterinary Parasitology 52, 6170.CrossRefGoogle ScholarPubMed
Konnai, S., Nakajima, C., Imamura, S., Yamada, S., Nishikado, H., Kodama, M., Onuma, M. and Ohashi, K. (2009). Suppression of cell proliferation and cytokine expression by HL-p36, a tick salivary gland-derived protein of Haemaphysalis longicornis. Immunology 126, 209219.CrossRefGoogle ScholarPubMed
Kotsyfakis, M., Anderson, J. M., Andersen, J. F., Calvo, E., Francischetti, I. M., Mather, T. N., Valenzuela, J. G. and Ribeiro, J. M. (2008). Cutting edge: Immunity against a “silent” salivary antigen of the Lyme vector Ixodes scapularis impairs its ability to feed. Journal of Immunology 181, 52095212.CrossRefGoogle ScholarPubMed
Kotsyfakis, M., Sá-Nunes, A., Francischetti, I. M., Mather, T. N., Andersen, J. F. and Ribeiro, J. M. (2006). Antiinflammatory and immunosuppressive activity of sialostatin L, a salivary cystatin from the tick Ixodes scapularis. Journal of Biological Chemistry 281, 2629826307.CrossRefGoogle Scholar
Makrides, S. C. and Ryan, U. S. (1998). Overview of the endothelium. In Thrombosis and Hemorrhage (ed. Loscalzo, J. and Schafer, A. I.), pp. 295306, 2nd Edn. Williams & Wilkins, Baltimore, MD, USA.Google Scholar
Mans, B. J., Gaspar, A. R., Louw, A. I. and Neitz, A. W. (1998). Purification and characterization of apyrase from the tick, Ornithodoros savignyi. Comparative Biochemistry and Physiology B – Biochemistry and Molecular Biology 120, 617624.CrossRefGoogle ScholarPubMed
Mans, B. J., Louw, A. I. and Neitz, A. W. (2002). Savignygrin, a platelet aggregation inhibitor from the soft tick Ornithodoros savignyi, presents the RGD integrin recognition motif on the Kunitz-BPTI fold. Journal of Biological Chemistry 277, 2137121378.CrossRefGoogle ScholarPubMed
Mans, B. J. and Ribeiro, J. M. (2008). Function, mechanism and evolution of the moubatin-clade of soft tick lipocalins. Insect Biochemistry and Molecular Biology 38, 841852.CrossRefGoogle ScholarPubMed
Maritz-Olivier, C., Stutzer, C., Jongejan, F., Neitz, A. W. and Gaspar, A. R. (2007). Tick anti-hemostatics: targets for future vaccines and therapeutics. Trends in Parasitology 23, 397407.CrossRefGoogle ScholarPubMed
Maxwell, S. S., Stoklasek, T. A., Dash, Y., Macaluso, K. R. and Wikel, S. K. (2005). Tick modulation of the in-vitro expression of adhesion molecules by skin-derived endothelial cells. Annals of Tropical Medicine and Parasitology 99, 661672.CrossRefGoogle ScholarPubMed
Murrell, A. and Barker, S. C. (2003). Synonymy of Boophilus Curtice, 1891 with Rhipicephalus Koch, 1844 (Acari: Ixodidae). Systematic Parasitology 56, 169172.CrossRefGoogle ScholarPubMed
Nazareth, R. A., Tomaz, L. S., Ortiz-Costa, S., Atella, G. C., Ribeiro, J. M., Francischetti, I. M. and Monteiro, R. Q. (2006). Antithrombotic properties of Ixolaris, a potent inhibitor of the extrinsic pathway of the coagulation cascade. Thrombosis and Haemostasis 96, 7–13.CrossRefGoogle ScholarPubMed
Ngai, P. K. and Chang, J. Y. (1991). A novel one-step purification of human alpha-thrombin after direct activation of crude prothrombin enriched from plasma. The Biochemical Journal 280, 805808.CrossRefGoogle ScholarPubMed
Prevot, P. P., Couvreur, B., Denis, V., Brossard, M., Vanhamme, L. and Godfroid, E. (2007). Protective immunity against Ixodes ricinus induced by a salivary serpin. Vaccine 25, 32843292.CrossRefGoogle ScholarPubMed
Reck, J. Jr., Berger, M., Terra, R. M. S., Marks, F. S., da Silva Vaz, I. Jr., Guimarães, J. A. and Termignoni, C. (2009). Effects of the tick Rhipicephalus (Boophilus) microplus infestation on the host hemostatic system. Research in Veterinary Science 86, 5662.CrossRefGoogle Scholar
Ribeiro, J. M. (1989). Role of saliva in tick/host interaction. Experimental and Applied Acarology 7, 1520.CrossRefGoogle Scholar
Ribeiro, J. M. (1995). Blood-feeding arthropods: live syringes or invertebrate pharmacologists? Infectious Agents and Diseases 4, 143152.Google ScholarPubMed
Ribeiro, J. M. and Francischetti, I. M. B. (2003). Role of arthropod saliva in blood-feeding: sialome and post-sialome perspectives. Annual Review of Entomology 48, 7388.CrossRefGoogle ScholarPubMed
Ribeiro, J. M., Schneider, M. and Guimarães, J. A. (1995). Purification and characterization of prolixin S (nitrophorin 2), the salivary anticoagulant of blood-sucking bug Rhodnius prolixus. The Biochemical Journal 308, 243249.CrossRefGoogle ScholarPubMed
Ricci, C. G., Pinto, A. F. M., Berger, M. and Termignoni, C. (2007). A thrombin inhibitor from the gut of Boophilus microplus ticks. Experimental and Applied Acarology 42, 291300.CrossRefGoogle ScholarPubMed
Rutter, J. M., Jones, G. W., Brown, G. T., Burrows, M. R. and Luther, P. D. (1975). Antibacterial activity in colostrum and milk associated with protection of piglets against enteric disease caused by K88-positive Escherichia coli. Infection and Immunity 13, 667676.CrossRefGoogle Scholar
Simmonds, R. E. and Lane, D. A. (1998). Regulation of coagulation. In: Thrombosis and Hemorrhage (ed. Loscalzo, J. and Schafer, A. I.), pp. 4576, 2nd Edn. Williams & Wilkins, Baltimore, MD, USA.Google Scholar
Steeves, E. B. and Allen, J. R. (1991). Tick resistance in mast cell-deficient mice: histological studies. International Journal for Parasitology 21, 265268.CrossRefGoogle ScholarPubMed
Timmons, S. and Hawiger, J. (1989). Isolation of human platelets by albumin gradient and gel filtration. Methods in Enzymology 169, 1121.CrossRefGoogle ScholarPubMed
Visseren, F. L., Bouwman, J. J., Bouter, K. P., Diepersloot, R. J., de Groot, P. H. and Erkelens, D. W. (2000). Procoagulant activity of endothelial cells after infection with respiratory viruses. Thrombosis and Haemostasis 84, 319324.Google ScholarPubMed
Vogel, G. M., Meuleman, D. G., Bourgondiën, F. G. and Hobbelen, P. M. (1989). Comparison of two experimental thrombosis models in rats: effects of four glycosaminoglycans. Thrombosis Research 54, 399410.CrossRefGoogle ScholarPubMed
Walker, D. H. (1998). Tick-transmitted infectious diseases in the United States. Annual Review of Public Health 19, 237269.CrossRefGoogle ScholarPubMed
Wikel, S. K. (1982). Immune responses to arthropods and theirs products. Annual Review of Entomology 27, 2148.CrossRefGoogle ScholarPubMed
Wikel, S. K. (1996 a). Immunology of the tick-host interface. In The Immunology of Host-Ectoparasitic Arthropod Relationships (ed. Wikel, S. K.), pp. 204231. CAB International, Wallingford, UK.Google Scholar
Wikel, S. K. (1996 b). Host immunity to ticks. Annual Review of Entomology 41, 122.CrossRefGoogle ScholarPubMed
Wikel, S. K., Ramachandra, R. N. and Bergman, D. K. (1996). Arthropod modulation of host immune responses. In The Immunology of Host-Ectoparasitic Arthropod Relationships (ed. Wikel, S. K.), pp. 107130. CAB International, Wallingford, UK.Google Scholar
Wikel, S. K. and Whelen, A. C. (1986). Ixodid-host immune interaction. Identification and characterization of relevant antigens and tick-induced host immunosuppression. Veterinary Parasitology 20, 149174.CrossRefGoogle ScholarPubMed
Willadsen, P. (1987). Immunological approaches to the control of ticks. International Journal for Parasitology 17, 671677.CrossRefGoogle Scholar
Willadsen, P., Bird, P., Cobon, G. S. and Hungerford, J. (1995). Commercialization of a recombinant vaccine against Boophilus microplus. Parasitology 110 (Suppl.), S43S50.CrossRefGoogle ScholarPubMed