TOWARDS THE DISCOVERY OF MOLECULES INVOLVED IN HEMATOPHAGOUS BLOOD FEEDING

AMINO R, MARTINS R, CAMPOS I¹, FALCÃO T, PROCÓPIO J², TANAKA A¹, DAN A³, BEIRÃO P³, PEREIRA M³AND SCHENKMAN S

Disciplina de Biologia Celular, UNIFESP

¹ Disciplina de Bioquímica, UNIFESP

² Departamento de Fisiologia, USP, São Paulo, SP.

³ Instituto de Ciências Biológicas, UFMG, Belo Horizonte, MG.

Triatoma infestans, one of the most important vectors of Chagas disease is an exclusively hematophagous insect. When the insect bites the vertebrate's skin it injects a cocktail of molecules with a broad range of redundant pharmacological activities to avoid host hemostatic and inflammatory responses triggered by biting.

We have detected and characterized in T. infestans three anticoagulant activities; an inhibitor of platelet aggregation induced by ADP, epinephrine and thrombin; proteases; hemolytic and pore forming activities; a neuraminidase; an inhibitor of sodium channel; molecules capable of inducing ileum and uterus contraction and peroxidase and fosfatase enzymatic activity. Most of these molecules are present in the saliva and are injected in the host's skin. Some of them are synthesized as inactive molecules and activated when the saliva is released. This is the case of a novel salivary serine protease that we named Triapsin, which is activated by limited proteolysis at the moment of insect bite.

From the insect anterior midgut we purified, cloned and expressed a potent thrombin inhibitor, named Infestin, showing that anti-hemostatic activities are also present in the digestive tract of the insect, preventing blood coagulation. The identification, characterization, cloning, and expression of these molecules in heterologous systems may provide new insights to understand anti-hemostatic mechanisms, the biology of hematophagous insect, and the discovery of novel molecules with pharmacological activities.

— ( September 14, 1999 ) .

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