Guianensin, a Simulium guianense salivary protein, has broad anti-hemostatic and anti-inflammatory properties
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F23%3A00574475" target="_blank" >RIV/60077344:_____/23:00574475 - isvavai.cz</a>
Result on the web
<a href="https://www.frontiersin.org/articles/10.3389/fimmu.2023.1163367/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fimmu.2023.1163367/full</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3389/fimmu.2023.1163367" target="_blank" >10.3389/fimmu.2023.1163367</a>
Alternative languages
Result language
angličtina
Original language name
Guianensin, a Simulium guianense salivary protein, has broad anti-hemostatic and anti-inflammatory properties
Original language description
BackgroundSalivary glands from blood-feeding arthropods secrete several molecules that inhibit mammalian hemostasis and facilitate blood feeding and pathogen transmission. The salivary functions from Simulium guianense, the main vector of Onchocerciasis in South America, remain largely understudied. Here, we have characterized a salivary protease inhibitor (Guianensin) from the blackfly Simulium guianense. Materials and methodsA combination of bioinformatic and biophysical analyses, recombinant protein production, in vitro and in vivo experiments were utilized to characterize the molecula mechanism of action of Guianensin. Kinetics of Guianensin interaction with proteases involved in vertebrate inflammation and coagulation were carried out by surface plasmon resonance and isothermal titration calorimetry. Plasma recalcification and coagulometry and tail bleeding assays were performed to understand the role of Guianensin in coagulation. ResultsGuianensin was identified in the sialotranscriptome of adult S. guianense flies and belongs to the Kunitz domain of protease inhibitors. It targets various serine proteases involved in hemostasis and inflammation. Binding to these enzymes is highly specific to the catalytic site and is not detectable for their zymogens, the catalytic site-blocked human coagulation factor Xa (FXa), or thrombin. Accordingly, Guianensin significantly increased both PT (Prothrombin time) and aPTT (Activated partial thromboplastin time) in human plasma and consequently increased blood clotting time ex vivo. Guianensin also inhibited prothrombinase activity on endothelial cells. We show that Guianensin acts as a potent anti-inflammatory molecule on FXa-induced paw edema formation in mice. ConclusionThe information generated by this work highlights the biological functionality of Guianensin as an antithrombotic and anti-inflammatory protein that may play significant roles in blood feeding and pathogen transmission.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10606 - Microbiology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Frontiers in Immunology
ISSN
1664-3224
e-ISSN
1664-3224
Volume of the periodical
14
Issue of the periodical within the volume
JULY
Country of publishing house
CH - SWITZERLAND
Number of pages
14
Pages from-to
1163367
UT code for WoS article
001026742300001
EID of the result in the Scopus database
2-s2.0-85165076962