Evidence map›Paper›PMID 24092749›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2013

Novel family of insect salivary inhibitors blocks contact pathway activation by binding to polyphosphate, heparin, and dextran sulfate.

Patricia H Alvarenga, Xueqing Xu, Fabiano Oliveira, Andrezza C Chagas, Clarissa R Nascimento, Ivo M B Francischetti, Maria A Juliano, Luiz Juliano, Julio Scharfstein, Jesus G Valenzuela and 2 more

Open access · greenAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.4field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 45 citations in OpenAlex.

  1. Review
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  7. Kinins and Their Receptors in Infectious Diseases.Pharmaceuticals (Basel, Switzerland) · 2020
    Review
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  20. What's behind a sand fly bite? The profound effect of sand fly saliva on host hemostasis, inflammation and immunity.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2014
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Patricia H AlvarengaFrom the Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Rockville, MD (P.H.A., X.X., F.O., A.C.C., I.M.B.F., J.G.V., J.M.C.R., J.F.A.); Laboratório de Bioquímica de Resposta ao Estresse, Instituto de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil (P.H.A.); Instituto Nacional de Ciência e Tecnologia em Entomologia Molecular (INCT-EM), Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil (P.H.A.); Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil (C.R.N., J.S.); and Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil (M.A.J., L.J.).
Xueqing Xu
Fabiano Oliveira
Andrezza C Chagas
Clarissa R Nascimento
Ivo M B Francischetti
Maria A Juliano
Luiz Juliano
Julio Scharfstein
Jesus G Valenzuela
José M C Ribeiro
John F Andersen
Universidade Federal do Rio de Janeiro · BR

Funding

Molecular approaches to understand vector-host and vector-pathogen interactionsZIAAI000932 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI VALENZUELA, JESUS · 2009 to 2025
$23.1M
Vector-Borne Diseases: Biology Of Vector Host RelationshipZIAAI000810 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI RIBEIRO, JOSE · 2009 to 2025
$20.8M
Vector-Borne Diseases: Molecular Mechanisms in Vector-Host InteractionsZIAAI001012 · NIAID · NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES · PI RIBEIRO, JOSE · 2009 to 2025
$9.4M
Intramural NIH HHS ZIA AI000932
6 · The paper itself

Abstract

objectivePolyphosphate and heparin are anionic polymers released by activated mast cells and platelets that are known to stimulate the contact pathway of coagulation. These polymers promote both the autoactivation of factor XII and the assembly of complexes containing factor XI, prekallikrein, and high-molecular-weight kininogen. We are searching for salivary proteins from blood-feeding insects that counteract the effect of procoagulant and proinflammatory factors in the host, including elements of the contact pathway. APPROACH AND

resultsHere, we evaluate the ability of the sand fly salivary proteins, PdSP15a and PdSP15b, to inhibit the contact pathway by disrupting binding of its components to anionic polymers. We attempt to demonstrate binding of the proteins to polyphosphate, heparin, and dextran sulfate. We also evaluate the effect of this binding on contact pathway reactions. We also set out to determine the x-ray crystal structure of PdSP15b and examine the determinants of relevant molecular interactions. Both proteins bind polyphosphate, heparin, and dextran sulfate with high affinity. Through this mechanism they inhibit the autoactivation of factor XII and factor XI, the reciprocal activation of factor XII and prekallikrein, the activation of factor XI by thrombin and factor XIIa, the cleavage of high-molecular-weight kininogen in plasma, and plasma extravasation induced by polyphosphate. The crystal structure of PdSP15b contains an amphipathic helix studded with basic side chains that forms the likely interaction surface.

conclusionsThe results of these studies indicate that the binding of anionic polymers by salivary proteins is used by blood feeders as an antihemostatic/anti-inflammatory mechanism.

Indexed as

AnimalsAnticoagulantsBlood CoagulationBlood Coagulation TestsCapillary PermeabilityCrystallography, X-RayDextran SulfateDose-Response Relationship, DrugFactor XIaFactor XIIaHeparinHumansInsect ProteinsKininogen, High-Molecular-WeightMiceModels, MolecularAnticoagulantsDextran SulfateFactor XIaFactor XIIaHeparinInsect ProteinsKininogen, High-Molecular-WeightPolyphosphatesPrekallikreinThrombinblood coagulation factor inhibitorsbradykininfactor XIfactor XIIinflammationkallikreinsleishmania

Identifiers

PMID24092749
PMCPMC4191670
OpenAlexW2112876304

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.