Chemokine Synergy and Neutrophil Function
Chemokine Synergy and Neutrophil Function
批准号:
9193997
负责人:
Krishna Rajarathnam
金额:
$23.25万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-06-16 至 2018-05-31
关键词:
AddressBacteriaBacterial InfectionsBindingBiochemicalBloodCXCL1 geneCXCL2 geneClinicalCommunicable DiseasesCytoplasmic GranulesDataDevelopmentDiseaseDoseEnzymesFocal InfectionFutureGTP-Binding ProteinsGrantHost DefenseHourIL8RB geneImmune systemInfectionInflammatoryInterleukin-8B ReceptorKnockout MiceKnowledgeMediatingMicrobeMolecularMusNeutrophil InfiltrationPeptide HydrolasesPeptidesPeripheralPeritonealPeritoneumPhenotypePhysiologicalPlayProcessPropertyReactive Oxygen SpeciesRecording of previous eventsRecruitment ActivityResearchResolutionRoleSignal PathwaySignal TransductionSiteSuperoxidesTestingTherapeuticTimeTissuesVariantbasebeta-arrestincell injurychemokinecytotoxicdesigndimerdrug developmentin vivoinsightkillingsmicrobialmonomerneutrophilnovelpathogenpublic health relevancereceptor mediated endocytosisresponsesuccesstherapeutic targettrafficking
中文摘要
先天免疫系统高度进化,通过招募中性粒细胞来对抗感染性病原体
英文摘要
The innate immune system is highly evolved to counter infectious pathogens by recruiting neutrophils in
a timely and coordinated manner. Multiple chemokines, expressed in response to infection, mediate this
process, by first recruiting neutrophils to the infection site, and then activating them to release cytotoxic
granule enzymes and superoxide to kill the offending microbe. Impaired recruitment and/or impaired
activation result in incomplete resolution of infection, whereas uncontrolled recruitment and/or sustained
activation result in destruction of healthy tissue and disease. At this time, the molecular mechanisms by
which coordinated action of chemokines mediate neutrophil function are not known. In mice, the
chemokines KC/CXCL1 and MIP2/CXCL2 coordinate neutrophil function. Our preliminary data show that
KC and MIP2 exist as monomers and dimers, and most interestingly, also as heterodimers. In this R21
exploratory grant, we will test the hypothesis that the structural and functional properties of KC and MIP2
and the crosstalk between KC and MIP2 play non-redundant roles in mediating neutrophil function. In
Aim 1, we will characterize how KC and MIP2 mediate peritoneal neutrophil recruitment to establish the
causal relationship between chemokine and neutrophil levels. More specifically, we will elucidate how
changes in monomer, dimer, and heterodimer levels influence neutrophil levels and define its activation
phenotype for microbial killing. In Aim 2, we will characterize the microbial killing activity of recruited
neutrophils by characterizing granule protease and superoxide activities. In Aim 3, we will characterize
the KC and MIP2 activities for CXCR2-mediated G-protein and β-arrestin signaling pathways and β-
arrestin mediated receptor endocytosis. Our hypothesis and research strategy for characterizing
chemokine crosstalk, and our preliminary data showing that recruitment profiles of KC and MIP2 can be
very different are novel. Successful completion of these studies will provide critical mechanistic insights
into the causal relationships between chemokine synergy and neutrophil phenotype, and serve as a
framework for future development of novel and effective therapeutic targets to treat infectious diseases.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Structural Basis of chemokine CXCL1 recognition with CXCR2 receptor
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批准号:10488181
-
项目类别:
-
资助金额:$20.0万
-
财政年份:2021
-
负责人:Krishna Rajarathnam
-
依托单位:
Structural Basis of chemokine CXCL1 recognition with CXCR2 receptor
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批准号:10218891
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项目类别:
-
资助金额:$25.29万
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财政年份:2021
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负责人:Krishna Rajarathnam
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依托单位:
Malvern MicroCal PEAQ Isothermal Titration Calorimeter
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批准号:9274599
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项目类别:
-
资助金额:$12.04万
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财政年份:2017
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负责人:Krishna Rajarathnam
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依托单位:
Chemokine CXCL17 and Mucosal Immunosurveillance
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批准号:8391500
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项目类别:
-
资助金额:$19.13万
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财政年份:2012
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负责人:Krishna Rajarathnam
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依托单位:
Chemokine CXCL17 and Mucosal Immunosurveillance
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批准号:8519289
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项目类别:
-
资助金额:$21.57万
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财政年份:2012
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负责人:Krishna Rajarathnam
-
依托单位:
Role of chemokine monomer-dimer equilibrium in innate immunity and inflammation
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批准号:7793450
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项目类别:
-
资助金额:$32.04万
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财政年份:2006
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负责人:Krishna Rajarathnam
-
依托单位:
Role of chemokine monomer-dimer equilibrium in innate immunity and inflammation
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批准号:7417794
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项目类别:
-
资助金额:$32.36万
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财政年份:2006
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负责人:Krishna Rajarathnam
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依托单位:
Role of chemokine monomer-dimer equilibrium in innate immunity and inflammation
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批准号:7221286
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项目类别:
-
资助金额:$32.99万
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财政年份:2006
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负责人:Krishna Rajarathnam
-
依托单位:
Role of chemokine monomer-dimer equilibrium in innate immunity and inflammation
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批准号:7083124
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项目类别:
-
资助金额:$32.28万
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财政年份:2006
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负责人:Krishna Rajarathnam
-
依托单位:
Role of chemokine monomer-dimer equilibrium in innate immunity and inflammation
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批准号:7616178
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项目类别:
-
资助金额:$32.36万
-
财政年份:2006
-
负责人:Krishna Rajarathnam
-
依托单位:
Role of chemokine monomer-dimer equilibrium in innate immunity and inflammation
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批准号:8060545
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项目类别:
-
资助金额:$31.72万
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财政年份:2006
-
负责人:Krishna Rajarathnam
-
依托单位:
Characterization of CCR5 Receptor N-terminal domain
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批准号:6843026
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项目类别:
-
资助金额:$22.65万
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财政年份:2004
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负责人:Krishna Rajarathnam
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依托单位:
Characterization of CCR5 Receptor N-terminal domain
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批准号:6907089
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项目类别:
-
资助金额:$22.65万
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财政年份:2004
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负责人:Krishna Rajarathnam
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依托单位:
Heparan Sulfate - Chemokine Interactions and Inflammation
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批准号:9277562
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项目类别:
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资助金额:$37.01万
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财政年份:--
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负责人:Krishna Rajarathnam
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依托单位:
Heparan Sulfate - Chemokine Interactions and Inflammation
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批准号:8380071
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项目类别:
-
资助金额:$44.12万
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财政年份:--
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负责人:Krishna Rajarathnam
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依托单位:
Heparan Sulfate - Chemokine Interactions and Inflammation
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批准号:8184151
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项目类别:
-
资助金额:$47.14万
-
财政年份:--
-
负责人:Krishna Rajarathnam
-
依托单位:
Heparan Sulfate - Chemokine Interactions and Inflammation
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批准号:8516577
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项目类别:
-
资助金额:$41.02万
-
财政年份:--
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负责人:Krishna Rajarathnam
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依托单位:
Heparan Sulfate - Chemokine Interactions and Inflammation
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批准号:8669116
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项目类别:
-
资助金额:$41.18万
-
财政年份:--
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负责人:Krishna Rajarathnam
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依托单位:
国内基金
海外基金
Segmented Filamentous Bacteria激活宿主免疫系统抑制其拮抗菌 Enterobacteriaceae维持菌群平衡及其机制研究
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批准号:81971557
-
项目类别:面上项目
-
资助金额:65.0万元
-
批准年份:2019
-
负责人:毛开睿
-
依托单位:
电缆细菌(Cable bacteria)对水体沉积物有机污染的响应与调控机制
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批准号:51678163
-
项目类别:面上项目
-
资助金额:64.0万元
-
批准年份:2016
-
负责人:许玫英
-
依托单位: