Hirudinas de la sanguijuela medicinal asiática Hirudinaria manillensis: iguales, pero diferentes

Blood coagulation in vertebrates is a complex mechanism that involves the precisely coordinated and regulated action of a cascade of factors in order to prevent excessive blood loss upon wounding. Any blood sucking ectoparasite, however, has to circumvent this mechanism to ensure the uptake of an adequate blood meal. Inhibitors of blood coagulation in the saliva are hence widespread among these animals. Thrombin as a key factor of blood coagulation is a prominent target of such inhibitors, and hirudin is probably the best known among the thrombin inhibitors. Hirudin was originally described in the genus Hirudo, but occurs in other leech genera like Hirudinaria and Macrobdella as well. Besides several isoforms of hirudin, a new class of putative leech saliva components, the hirudin-like factors (HLFs), was identified in both genera Hirudo and Hirudinaria. Here, we describe the expression, purification, and functional characterization of three HLFs (HLF5, 6, and 8, respectively) and two additional hirudins (HM3 and HM4) of Hirudinaria manillensis. While HLF6 lacked any inhibitory activity on thrombin, HLF5 as well as HLF8 clearly exhibited anticoagulatory properties. The inhibitory activity of HLF5 and HLF8, however, was much lower compared with both HM3 and HM4 of Hirudinaria manillensis as well as the hirudin variants 1 (HV1) and 2 (HV2) of Hirudo medicinalis. Neither an inhibition of trypsin nor a platelet aggregation was caused by HLF8. Our data indicates the presence of two classes (rather than isoforms) of hirudins in Hirudinaria manillensis with markedly different inhibitory activity on human thrombin.

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Se expresaron, purificaron y caracterizaron funcionalmente tres factores similares a la hirudina (HLF5, HLF6, HLF8) y las hirudinas HM3 y HM4 de Hirudinaria manillensis. HLF6 no inhibió la trombina; HLF5 y HLF8 mostraron propiedades anticoagulantes, aunque mucho menores que HM3 y HM4 y las variantes HV1 y HV2 de Hirudo medicinalis; HLF8 no inhibió la tripsina ni causó agregación plaquetaria. Los datos indican dos clases de hirudinas en H. manillensis con actividad inhibidora marcadamente distinta sobre la trombina humana.

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