Evidence map›Paper›PMID 33915031›Full record

ArticleJournal of thrombosis and haemostasis : JTH2021

Differential regulation of the platelet GPIb-IX complex by anti-GPIbβ antibodies.

M Edward Quach, Wenchun Chen, Yingchun Wang, Hans Deckmyn, François Lanza, Bernhard Nieswandt, Renhao Li

Open access · bronzeAbstract read
In one paragraph

Article in Journal of thrombosis and haemostasis : JTH, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

10 citing papers in PubMed, 14 citations in OpenAlex.

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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

7 authors at 4 institutions in 4 countries.

M Edward QuachAflac Cancer and Blood Disorders Center, Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.ORCID 0000-0001-7791-4562
Wenchun ChenAflac Cancer and Blood Disorders Center, Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.
Yingchun WangAflac Cancer and Blood Disorders Center, Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.
Hans DeckmynLaboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium.
François LanzaUniversité de Strasbourg, INSERM, BPPS UMR-S1255, Strasbourg, France.
Bernhard NieswandtRudolf Virchow Center, Julius Maximilian University of Wurzburg, Würzburg, Germany.
Renhao LiAflac Cancer and Blood Disorders Center, Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.ORCID 0000-0002-5806-5080
Emory University · USInserm · FRResearch Institute for Chromatography · BEUniversity of Würzburg · DE

Funding

Structure and Function of Platelet Glycoprotein lb-IX-V ComplexR01HL082808 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI LI, RENHAO · 2006 to 2023
$6.4M
Cryo-ET structural studies of plateletsR21HL146299 · NHLBI · EMORY UNIVERSITY · PI LI, RENHAO, WRIGHT, ELIZABETH R · 2019 to 2020
$429k
A multidisciplinary approach to elucidate the pathophysiology of thrombocytopeniaF31HL134241 · NHLBI · EMORY UNIVERSITY · PI QUACH, MICHAEL IAN · 2016 to 2018
$132k
NHLBI NIH HHS F31 HL134241NHLBI NIH HHS HL082808NHLBI NIH HHS HL134241NHLBI NIH HHS HL146299NHLBI NIH HHS R01 HL082808NHLBI NIH HHS R21 HL146299
6 · The paper itself

Abstract

backgroundPlatelets' initial recognition of endothelial damage proceeds through the interaction between collagen, plasma von Willebrand factor (VWF), and the platelet glycoprotein (GP)Ib-IX complex (CD42). The GPIb-IX complex consists of one GPIbα, one GPIX, and two GPIbβ subunits. Once platelets are immobilized to the subendothelial matrix, shear generated by blood flow unfolds a membrane-proximal mechanosensory domain (MSD) in GPIbα, exposing a conserved trigger sequence and activating the receptor. Currently, GPIbα appears to solely facilitate ligand-induced activation because it contains both the MSD and the binding sites for all known ligands to GPIb-IX. Despite being positioned directly adjacent to the MSD, the roles of GPIbβ and GPIX in signal transduction remain murky.

objectivesTo characterize a novel rat monoclonal antibody 3G6 that binds GPIbβ.

methodsEffects of 3G6 on activation of GPIb-IX are characterized in platelets and Chinese hamster ovary cells expressing GPIb-IX (CHO-Ib-IX) and compared with those of an inhibitory anti-GPIbβ antibody, RAM.1.

resultsBoth RAM.1 and 3G6 bind to purified GPIbβ and GPIb-IX with high affinity. 3G6 potentiates GPIb-IX-associated filopodia formation in platelets or CHO-Ib-IX when they adhere VWF or antibodies against the ligand-binding domain (LBD) of GPIbα. Pretreatment with 3G6 also increased anti-LBD antibody-induced GPIb-IX activation. Conversely, RAM.1 inhibits nearly all GPIb-IX-related signaling in platelets and CHO-Ib-IX cells.

conclusionsThese data represent the first report of a positive modulator of GPIb-IX activation. The divergent modulatory effects of 3G6 and RAM.1, both targeting GPIbβ, strongly suggest that changes in the conformation of GPIbβ underlie outside-in activation via GPIb-IX.

Indexed as

Blood PlateletsPlatelet Glycoprotein GPIb-IX ComplexAnimalsBinding SitesCHO CellsCricetinaeCricetulusHumansRatsvon Willebrand FactorPlatelet Glycoprotein GPIb-IX Complexvon Willebrand Factorbiomechanicsfilopodiaglycoprotein Ib-IX complexmicroscopyplatelet activation

Identifiers

PMID33915031
PMCPMC8324530
OpenAlexW3158905677

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.