Penthalaris, a novel recombinant five-Kunitz tissue factor pathway inhibitor (TFPI) from the salivary gland of the tick vector of Lyme disease, Ixodes scapularis.
Research article published in Thrombosis and haemostasis (2004)
Abstract
Tick saliva is a rich source of molecules with antiinflammatory, antihemostatic and immunosupressive properties. In this paper, a novel tick salivary gland cDNA with sequence homology to tissue factor pathway inhibitor (TFPI) and coding for a protein called Penthalaris has been characterized from the Lyme disease vector, Ixodes scapularis. Penthalaris is structurally unique and distinct from TFPI or TFPI-like molecules described so far, including Ixolaris, NAPc2, TFPI-1 and TFPI-2. Penthalaris is a 308-amino-acid protein (35 kDa, pI 8.58) with 12 cysteine bridges and 5 tandem Kunitz domains. Recombinant Penthalaris was expressed in insect cells and shown to inhibit factor VIIa (FVIIa)/tissue factor(TF)-induced factor X (FX) activation with an IC50 of approximately 100 pM. Penthalaris tightly binds both zymogen FX and enzyme FXa (exosite), but not FVIIa, as demonstrated by column gel-filtration chromatography. At high concentrations, Penthalaris attenuates FVIIa/TF-induced chromogenic substrate (S2288) hydrolysis and FIX activation. In the presence of DEGR-FX or DEGR-FXa, but not des-Gla-DEGR-FXa as scaf-folds, tight and stoichiometric inhibition of FVIIa/TF was achieved. In addition, Penthalaris blocks cell surface-mediated FXa generation by monomer (de-encrypted), but not dimer (encrypted) TF in HL-60 cells. Penthalaris may act in concert with Ixolaris and other salivary anti-hemostatics in order to help ticks to successfully feed on blood. Penthalaris is a novel anticoagulant and a tool to study FVIIa/TF-initiated biologic processes.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Tick saliva is a rich source of molecules with antiinflammatory, antihemostatic and immunosupressive properties.
Por qué esto importa para la hirudoterapia
Este estudio caracterizó Penthalaris, un nuevo inhibidor de la vía del factor tisular con cinco dominios Kunitz clonado de la glándula salival de la garrapata Ixodes scapularis, y demostró que la proteína recombinante inhibe la activación del Factor X inducida por FVIIa/factor tisular (IC50 ~100 pM) y se une al factor X/Xa en un exositio. Cabe señalar claramente que se trata de un anticoagulante salival de garrapata, no de una molécula de sanguijuela medicinal (Hirudo), por lo que es relevante para ASH únicamente por analogía, como parte del campo más amplio de descubrimiento de fármacos del secretoma de organismos hematófagos que justifica por qué se estudia la saliva de la sanguijuela, y no como evidencia directa de la hirudoterapia. El trabajo consiste en farmacología molecular y celular preclínica (expresión recombinante en células de insectos, ensayos enzimáticos in-vitro, estudios de superficie celular HL-60) sin pruebas clínicas y, a pesar de situarse en el mismo campo de descubrimiento de anticoagulantes, no debe presentarse como un respaldo a la terapia con sanguijuelas.
Citación
Penthalaris, a novel recombinant five-Kunitz tissue factor pathway inhibitor (TFPI) from the salivary gland of the tick vector of Lyme disease, Ixodes scapularis.
Francischetti IM et al. · Thrombosis and haemostasis, 2004
Contexto clínico relacionado
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Añadido a la biblioteca ASH: May 28, 2026 · Última actualización del sitio: June 18, 2026