LOX-1 as a protective countermeasure in response to lung infection
LOX-1 as a protective countermeasure in response to lung infection
批准号:
10677924
负责人:
Lee Quinton
金额:
$77.45万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-06-15 至 2027-05-31
关键词:
AcuteAcute Lung InjuryAcute Respiratory Distress SyndromeAddressAlveolarAlveolar MacrophagesAlveolitisAnti-Inflammatory AgentsAtherosclerosisAutopsyBiologicalBiological ProcessBiologyCardiovascular DiseasesCellsCessation of lifeCirculationClinicalClinical PathwaysDataEmigrationsEndotheliumFeedbackFlow CytometryGene Expression ProfileGenesGoalsHematopoieticHomeostasisHumanImmuneImmunityImmunologic ReceptorsInfectionInflammationInflammatoryInjuryInterruptionInterventionLearningLectinLectin ReceptorsLeukocytesLigandsLipidsLow Density Lipoprotein ReceptorLower Respiratory Tract InfectionLungLung infectionsMacrophageMembrane ProteinsMessenger RNAMorbidity - disease rateMusMyelogenousMyeloid CellsMyeloid-derived suppressor cellsNeutrophil InfiltrationOutcomePPAR gammaPatient-Focused OutcomesPatientsPilot ProjectsPneumoniaPopulationProteinsPublic HealthPulmonary InflammationRXRRespiratory Tract InfectionsRiskRoleSepsisShapesSignal TransductionSiteSourceSpecimenSystemTestingTissuesVascular EndotheliumViralalveolar homeostasisdisorder riskfortificationgranulocyteimmunopathologyimprovedin vivolung injurymortalityneutrophilnoveloxidized low density lipoproteinprogramsprotective effectprotein expressionreceptorrecruitrepositoryresilienceresponsescavenger receptorselective expressionsepsis induced ARDStissue injuryvascular injuryvirtual
中文摘要
摘要
英文摘要
Abstract
Pneumonia is a leading cause of morbidity and mortality worldwide, due in large part to the onset of acute
respiratory distress syndrome (ARDS), for which there is no greater origin. Imbalances of the biological
processes controlling immunity and tissue integrity increase the likelihood that lung infections progress to
pneumonia, demanding a better understanding of when, where, and how host signals integrate to confer
protection. Here we propose the scavenger receptor lectin-like oxidized low-density lipoprotein receptor-1
(LOX-1) as a regulatory node for shaping inflammation in the pneumonic lung. While this receptor has well-
established roles in promoting vascular injury in patients with atherosclerosis, its function in the lungs is
unknown. Our preliminary results from both mice and humans indicate substantial accumulation of LOX-1 in
pneumonic lungs. Moreover, our mouse studies reveal that LOX-1 in the airspace compartment, particularly
that originating from hematopoietic cells, dampens immunopathology in the infected lung. This contrasts the
harmful roles of LOX-1 during cardiovascular disease, implicating the alveolar milieu as a unique niche for
LOX-1-dependent tissue fortification. Although LOX-1 has never been investigated in the context of lung
infections, we posit that its expression by alveolar macrophages and neutrophils serves as a countermeasure
to dampen pneumonia-induced inflammation and maintain tissue integrity. Therefore, we will test the central
hypothesis that LOX-1 on airspace myeloid cells bolsters tissue protection in response to lung infection. This
will be addressed by pursuing the following 3 aims: Aim 1) Test the hypothesis hematopoietic cellular subsets
prominently contribute to LOX-1-driven tissue protection in the infected lung; Aim 2) Test the hypothesis that
LOX-1 promotes efferocytosis and repolarization in alveolar macrophages to limit immunopathology during
pneumonia; and Aim 3) Test the hypothesis that LOX-1 guides alveolar neutrophils towards an MDSC-like
state through altered lipid handling and anti-inflammatory feedback, countering infection-induced injury. Our
proposed studies will leverage complementary in vivo and ex vivo approaches in order to reveal basic
biological mechanisms of tissue homeostasis during pneumonia, paving the way for novel clinical interventions
in patients with or at risk for this disease.
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LOX-1 as a protective countermeasure in response to lung infection
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批准号:10690260
-
项目类别:
-
资助金额:$70.35万
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财政年份:2022
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负责人:Lee Quinton
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依托单位:
Liver-derived protection during pneumonia and sepsis
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批准号:9309668
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项目类别:
-
资助金额:$31.67万
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财政年份:2017
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负责人:Lee Quinton
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依托单位:
The Biology of LIF During Pneumonia
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批准号:8681505
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项目类别:
-
资助金额:$40.11万
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财政年份:2012
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负责人:Lee Quinton
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依托单位:
The Biology of LIF During Pneumonia
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批准号:9066165
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项目类别:
-
资助金额:$40.93万
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财政年份:2012
-
负责人:Lee Quinton
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依托单位:
Inducible epithelial resilience during pneumonia
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批准号:9381339
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项目类别:
-
资助金额:$41.13万
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财政年份:2012
-
负责人:Lee Quinton
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依托单位:
The Biology of LIF During Pneumonia
-
批准号:8526540
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项目类别:
-
资助金额:$38.96万
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财政年份:2012
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负责人:Lee Quinton
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依托单位:
The Biology of LIF During Pneumonia
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批准号:8371498
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项目类别:
-
资助金额:$40.93万
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财政年份:2012
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负责人:Lee Quinton
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依托单位:
Lung-Liver Axis During Pneumonia
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批准号:8133529
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项目类别:
-
资助金额:$24.9万
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财政年份:2010
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负责人:Lee Quinton
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依托单位:
Lung-Liver Axis During Pneumonia
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批准号:8288115
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项目类别:
-
资助金额:$24.65万
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财政年份:2010
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负责人:Lee Quinton
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依托单位:
Lung-Liver Axis During Pneumonia
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批准号:8076424
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项目类别:
-
资助金额:$24.9万
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财政年份:2010
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负责人:Lee Quinton
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依托单位:
Lung-Liver Axis During Pneumonia
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批准号:7509539
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项目类别:
-
资助金额:$10.2万
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财政年份:2008
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负责人:Lee Quinton
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依托单位:
Lung-Liver Axis During Pneumonia
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批准号:7652463
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项目类别:
-
资助金额:$10.4万
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财政年份:2008
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负责人:Lee Quinton
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依托单位:
海外基金