Role of Ezrin in Macrophages
Ezrin 在巨噬细胞中的作用
基本信息
- 批准号:10427446
- 负责人:
- 金额:$ 63.23万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-01 至 2026-06-30
- 项目状态:未结题
- 来源:
- 关键词:Actin-Binding ProteinActinsAdhesionsAffectAlveolarAsthmaBacteriaBacterial InfectionsBindingBiologyBlood CellsCalpainCell AdhesionCell membraneCell physiologyCellsChronic Obstructive Pulmonary DiseaseCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorCytoskeletonDataDiseaseEventExtracellular MatrixFailureFunctional disorderGatekeepingGoalsHealthHost DefenseIgG ReceptorsImmune System DiseasesImmune responseImmune signalingImpairmentIndividualInfectionInflammationInflammatoryInflammatory ResponseIntegrinsKnock-outKnockout MiceLipopolysaccharidesLungLung diseasesLung immune responseLung infectionsMembrane ProteinsModelingMolecularMorbidity - disease rateMucous body substanceMusObstructionPI3K/AKTPathologicPathway interactionsPhagocytesPhagocytosisPopulationProtein FamilyPseudomonas aeruginosaPublishingPulmonary Cystic FibrosisPulmonary InflammationReportingResearchResearch PersonnelResolutionRespiratory Tract InfectionsRoleSeverity of illnessShapesSignal TransductionStaphylococcus aureusStimulusStructure of parenchyma of lungTestingTissuesWorkbactericidebasecell cortexchronic inflammatory lung diseasecystic fibrosis mousecystic fibrosis patientsezrinfightingimmune functionimmunoregulationimprovedin vivo Modelinnovationinterstitialmacrophagemembermicroorganismmoesinmonocytemortalitymouse modelparticlepathogenradixin proteinrecruitresponsetargeted treatmenttherapeutic target
项目摘要
PROJECT SUMMARY
Macrophages (MΦs) kill microorganisms, engulf dead cells and debris, and regulate the immune response. They
are thus gatekeepers of tissue health, including the lungs. The lung-tissue-resident MΦs (TR-MΦs) are the
interstitial and alveolar MΦs, which have complementary but distinct functions. In response to infections, lungs
are rapidly populated by waves of Ly6C+ circulating monocytes. In concert with TR-MΦs, these monocytes fight
the infection, then facilitate the resolution of the inflammatory response. Many chronic lung inflammatory
diseases, including cystic fibrosis (CF), are associated with dysregulated MΦ function. Our long- term goal is to
understand how different lung MΦ populations contribute to lung hyper-inflammation and infection and to
elucidate the biology of these distinct cell populations. The objective of this proposal is to characterize ezrin’s
role in monocyte/MΦ function. Our central hypothesis is that ezrin controls monocyte/MΦ cortical actin
organization and signal transduction events in response to inflammatory/infectious stimuli. These cellular
changes allow the MΦs to spread, move, phagocytize, and survive, thus shaping the magnitude and quality of
the lung immune response to infections. The rationale for these studies is that low ezrin levels have been found
in MΦs from patients with CF (our work). Other investigators have also reported low ezrin levels in blood cells
from individuals with asthma. Thus, by elucidating the molecular mechanism by which ezrin shapes lung MΦ
functions, we could identify potential therapeutic targets for lung diseases. Our specific aims will test the following
hypotheses: (Aim 1) ezrin is required for the signaling that drives MΦs to adhere to the lung extracellular matrix
and to differentiate in response to LPS; (Aim 2) ezrin is needed for efficient phagocytosis of Staphylococcus
aureus and Pseudomonas aeruginosa, two microorganisms that CF patients fail to efficiently eradicate from their
lungs; (Aim 3) the acquired “cellular ezrin low-state” inactivated CF MΦs is central to their uncontrolled immune
signaling and reduced phagocytosis. The contribution is significant since very little is known about ezrin’s role in
regulating lung MΦ activation. Our proposed research is innovative because we will use an unprecedented
mouse model in which ezrin is knocked out in monocytes and MΦs. Thus, the proposed studies will investigate in
depth the consequences of ezrin loss in monocytes and MΦs during lung infection and inflammation.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Emanuela Marina Bruscia其他文献
Emanuela Marina Bruscia的其他文献
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{{ truncateString('Emanuela Marina Bruscia', 18)}}的其他基金
Pathogenic monocyte response to chronic lung inflammation in cystic fibrosis
致病性单核细胞对囊性纤维化慢性肺部炎症的反应
- 批准号:
10545042 - 财政年份:2022
- 资助金额:
$ 63.23万 - 项目类别:
Pathogenic monocyte response to chronic lung inflammation in cystic fibrosis
致病性单核细胞对囊性纤维化慢性肺部炎症的反应
- 批准号:
10366464 - 财政年份:2022
- 资助金额:
$ 63.23万 - 项目类别:
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Priority Programmes
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