AvaliaÃ§Ã£o da atividade farmacolÃ³gica de uma famÃlia de proteÃnas ligantes de quimiocinas derivada da saliva de carrapato
The chemokines are involved in physiologic events and pathologic process of many diseases. Then, they are potential targets to new therapeutics strategies. Several virus and Schistosoma mansoni subvert their host immune system by producing proteins that selectivelyneutralize the chemokines that mediate inflammatory process. The ticks present in their saliva many agents, such as chemokines binding proteins that allow them to feed for long periods of time without are detected by immunologic systems of host. Through cDNA library from thesalivary glands of the tick Rhipicephalus sanguineus were identificated three chemokines binding proteins called, Evasins, that dont have structural homology with any known proteins. Unlike viral and Schistosoma mansoni chemokines binding proteins this familypresent high selectivity to their ligands. In vitro studies showed that Evasin-1 binds to MIP-1a/CCL3, MIP-1b/CCL4 and PARC/CCL18. The Evasin-3 binds to IL-8/CXCL8 and GRO-a/CXCL1 and their murine homologous (KC/CXCL1-3 and MIP-2/CXCL1-2). The Evasin-4binds to eotaxin/CCL11 and RANTES/CCL5. In the present work we evaluated the pharmacological activity of evasins in different inflammation models. The Evasin-1 inhibited the cellular recruitment induced by MIP-1a/CCL3 and decreased the inflammation in delayed type hipersensiblity models and bleomycin induced pulmonary fibrosis. In a similar way, Evasin-3 and Evasin-4 prevented the neutrophil and eosinophil influx, respectively, induced by chemothatic factors or by antigen in sensibilized animals. Then, these chemokines bindingproteins, which are smaller than the natural camel antibodies that present only heavy chain, have pharmacological activity in vivo and are effective in reducing inflammation in animal models. The evasins could be relevant anti-inflammatory strategies in the future and useful for the creation of new scafolls through rational design.
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Advisor:Mauro Martins Teixeira; Denise Carmona Cara Machado; Deborah Aparecida Negrao Correa; Marco AurÃ©lio Martins; Andre Talvani
School:Universidade Federal de Minas Gerais
Source Type:Master's Thesis
Keywords:fisiologia teses quimiocinas inflamaã§ã£o
Date of Publication:12/13/2007