Evidence map›Paper›PMID 41643555›Full record

ArticleBiochemical and biophysical research communications2026

NLRP3 inflammasome-mediated platelet hyperreactivity in sickle cell mice is targetable by BTK inhibition.

Sebastian Vogel, Sayuri Kamimura, Eric Nguyen, Meghann Smith, Luis E F Almeida, Patricia Zerfas, Kapil Bharti, Christian Combs, Michelly Sampaio de Melo, Zenaide M N Quezado

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In one paragraph

Article in Biochemical and biophysical research communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Sebastian VogelDepartment of Perioperative Medicine, National Institutes of Health Clinical Center, NIH, USA.
Sayuri KamimuraDepartment of Perioperative Medicine, National Institutes of Health Clinical Center, NIH, USA.
Eric NguyenOcular and Stem Cell Translational Research Section, Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, USA.
Meghann SmithDepartment of Perioperative Medicine, National Institutes of Health Clinical Center, NIH, USA.
Luis E F AlmeidaDepartment of Perioperative Medicine, National Institutes of Health Clinical Center, NIH, USA.
Patricia ZerfasOffice of Research Services, Office of the Director, NIH, USA.
Kapil BhartiOcular and Stem Cell Translational Research Section, Ophthalmic Genetics and Visual Function Branch, National Eye Institute, NIH, USA.
Christian CombsLight Microscopy Core, National Heart, Lung, and Blood Institute, NIH, USA.
Michelly Sampaio de MeloHematology Laboratory Service, Department of Laboratory Medicine, National Institutes of Health Clinical Center, NIH, USA.
Zenaide M N QuezadoDepartment of Perioperative Medicine, National Institutes of Health Clinical Center, NIH, USA. Electronic address: zquezado@nih.gov.

Funding

Neurobiology of pain and behavior changes associated with rare diseases and developmental disabilitiesZIACL090052 · CLC · CLINICAL CENTER · PI QUEZADO, ZENAIDE · 2017 to 2025
$0k
Pathobiology of pain in sickle cell diseaseZIACL090053 · CLC · CLINICAL CENTER · PI QUEZADO, ZENAIDE · 2017 to 2025
$0k
Intramural NIH HHS ZIA CL090052Intramural NIH HHS ZIA CL090053
6 · The paper itself

Abstract

The platelet nucleotide-binding domain leucine-rich repeat-containing protein 3 (NLRP3) inflammasome is upregulated in sickle cell disease (SCD) and promotes platelet aggregation. We previously identified Bruton tyrosine kinase (BTK) as a critical regulator of the platelet NLRP3 inflammasome. However, whether NLRP3 contributes to platelet function beyond aggregation in SCD and whether these effects can be modulated through BTK inhibition, has been incompletely understood. Here, we show that platelet secretion, platelet spreading, platelet aggregation, and in vitro thrombus formation in response to collagen are elevated in SCD mice and are reduced following treatment of mice with the NLRP3 inhibitor MCC950 or the BTK inhibitor ibrutinib. The NLRP3 activator nigericin partially reversed the inhibitory effects of ibrutinib across all platelet function assays. Together, we identify the NLRP3 inflammasome as a critical mediator of platelet hyperreactivity in SCD mice, which can be targeted via BTK inhibition.

Indexed as

Agammaglobulinaemia Tyrosine KinaseAnemia, Sickle CellBlood PlateletsInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinProtein Kinase InhibitorsAdenineAnimalsFuransHeterocyclic Compounds, 4 or More RingsIndenesMiceMice, Inbred C57BLNigericinPiperidinesPlatelet AggregationAdenineAgammaglobulinaemia Tyrosine KinaseBtk protein, mouseFuransHeterocyclic Compounds, 4 or More RingsibrutinibIndenesInflammasomesN-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamideNigericinNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mousePiperidinesProtein Kinase InhibitorsPyrazolesPyrimidinesSulfonamidesSulfonesBruton tyrosine kinaseNLRP3 inflammasomePlateletsSickle cell disease

Identifiers

PMID41643555
PMCPMC12969050

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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.