An Ixodes persulcatus Inhibitor of Plasmin and Thrombin Hinders Keratinocyte Migration, Blood Coagulation, and Endothelial Permeability.

Autor: Berger M; Tick-Pathogen Transmission Unit, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA; Centro de Pesquisa Experimental, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil., Rosa da Mata S; Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil., Pizzolatti NM; Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil., Parizi LF; Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil., Konnai S; Laboratory of Infectious Diseases, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan., da Silva Vaz I Jr; Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Faculdade de Veterinária, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Instituto Nacional de Ciência e Tecnologia-Entomologia Molecular, Rio de Janeiro, Brazil., Seixas A; Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil; Instituto Nacional de Ciência e Tecnologia-Entomologia Molecular, Rio de Janeiro, Brazil. Electronic address: adrianaseixas@ufcspa.edu.br., Tirloni L; Tick-Pathogen Transmission Unit, Laboratory of Bacteriology, National Institute of Allergy and Infectious Diseases, Hamilton, Montana, USA. Electronic address: lucas.tirloni@nih.gov.
Jazyk: angličtina
Zdroj: The Journal of investigative dermatology [J Invest Dermatol] 2024 May; Vol. 144 (5), pp. 1112-1123.e7. Date of Electronic Publication: 2023 Nov 22.
DOI: 10.1016/j.jid.2023.10.026
Abstrakt: The skin is the first host tissue that the tick mouthparts, tick saliva, and a tick-borne pathogen contact during feeding. Tick salivary glands have evolved a complex and sophisticated pharmacological arsenal, consisting of bioactive molecules, to assist blood feeding and pathogen transmission. In this work, persulcatin, a multifunctional molecule that targets keratinocyte function and hemostasis, was identified from Ixodes persulcatus female ticks. The recombinant persulcatin was expressed and purified and is a 25-kDa acidic protein with 2 Kunitz-type domains. Persulcatin is a classical tight-binding competitive inhibitor of proteases, targeting plasmin (K i : 28 nM) and thrombin (K i : 115 nM). It blocks plasmin generation on keratinocytes and inhibits their migration and matrix protein degradation; downregulates matrix metalloproteinase 2 and matrix metalloproteinase 9; and causes a delay in blood coagulation, endothelial cell activation, and thrombin-induced fibrinocoagulation. It interacts with exosite I of thrombin and reduces thrombin-induced endothelial cell permeability by inhibiting vascular endothelial-cadherin disruption. The multifaceted roles of persulcatin as an inhibitor and modulator within the plasminogen-plasmin system and thrombin not only unveil further insights into the intricate mechanisms governing wound healing but also provide a fresh perspective on the intricate interactions between ticks and their host organisms.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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