Neutrophil Nox2 controls mononuclear cell functions in inflammation; role in CGD
Neutrophil Nox2 controls mononuclear cell functions in inflammation; role in CGD
批准号:
10228694
负责人:
DONNA L BRATTON
金额:
$62.65万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-09-18 至 2023-08-31
关键词:
AcuteAddressAdoptive TransferAnimal ModelAnimalsAnti-Inflammatory AgentsAutoimmunityBacteriaBehaviorBody Weight decreasedCell DeathCell physiologyCellsChronicChronic Granulomatous DiseaseCoculture TechniquesColitisComplexDataDevelopmentDiseaseEmigrationsEventExcisionFailureGeneticGranulomaHumanImmunologic Deficiency SyndromesInfectionInflammationInflammatoryInflammatory ResponseKnock-outLeadLesionLeukocytesLinkLocationMalaiseMediatingModelingMolecular AbnormalityMononuclearMusMutateMutationNADPH OxidaseOmentumOxidasesPatientsPeritoneumPhagocytesProcessPropertyPublic HealthRecruitment ActivityResolutionRoleSignal TransductionSiteTestingWild Type Mousedesigneffective therapyexperimental studyfightingfungusgranulocytehuman modelin vivomacrophagemonocytemouse modelneutrophilnovelnovel strategiesnovel therapeutic interventionpreventrecruitsystemic inflammatory responsewound healing
中文摘要
项目概要/摘要
慢性肉芽肿病(CGD)是一种罕见的,但破坏性的疾病,已知的遗传异常,
吞噬细胞(白色血细胞)氧化酶。除了免疫缺陷(无法对抗某些细菌)之外,
和真菌),这种疾病的患者往往有复杂的和了解不多的异常,炎症
过程表现为结肠炎、伤口愈合不良、阻塞性肉芽肿和自身免疫。重要的是,
对于许多这些炎性后果缺乏明确适用和有效的治疗。
我们在人类X连锁CGD动物模型中的研究清楚地指出,在炎症过程中,
两种不同类型的吞噬细胞之间的过程,都与突变的氧化酶:中性粒细胞(或
粒细胞)和单核吞噬细胞。具体来说,我们已经表明,虽然CGD中性粒细胞是
无法控制单核细胞的募集、成熟、炎症编程和处置,
在炎症部位的吞噬细胞,正常中性粒细胞的直接引入能够恢复这些
活动和事件在体内。因此,来自正常嗜中性粒细胞的信号协调了
单核吞噬细胞在炎症的正常发展和消退的每一步。是
假设识别正常中性粒细胞提供的这些信号可以提供新的治疗方法,
战略布局使用小鼠模型和中性粒细胞及其产物的过继转移以及细胞共培养,
培养实验(离体),该建议旨在定义异常的潜在机制,
CGD中单核吞噬细胞的行为和CGD中性粒细胞缺乏的精确过程,
通过增加正常的中性粒细胞来克服。对这些问题的界定有望导致新的方法,
治疗CGD和可能的其他慢性炎性病症。
.
英文摘要
Project Summary / Abstract
Chronic granulomatous disease (CGD) is a rare, but devastating, disease with known genetic abnormalities in
the phagocyte (white blood cell) oxidase. In addition to immunodeficiency (the inability to fight certain bacteria
and fungi), patients with this disease often have complex and poorly understood abnormalities in inflammatory
processes manifest as colitis, poor wound healing, obstructing granuloma, and autoimmunity. Importantly,
there is a lack of clearly applicable and effective treatments for many of these inflammatory consequences.
Our studies in an animal model of human X-linked CGD clearly point to abnormal crosstalk during inflammatory
processes between two different types of phagocytes, both with the mutated oxidase: neutrophils (or
granulocytes) and mononuclear phagocytes. Specifically, we have shown that whereas CGD neutrophils were
unable control the recruitment, maturation, inflammatory programming and disposal of the mononuclear
phagocytes at sites of inflammation, the direct introduction of normal neutrophils was able to restore these
activities and events in vivo. As such, signals from normal neutrophils orchestrate the activities of the
mononuclear phagocytes at each step in the normal development and resolution of inflammation. It is
hypothesized that identifying these signals provided by normal neutrophils could provide new therapeutic
strategies. Using the murine model and adoptive transfers of neutrophils and their products as well as cell co-
culture experiments (ex vivo), this proposal aims to define the mechanisms underlying the abnormal
mononuclear phagocyte behavior in CGD and the precise processes lacking in CGD neutrophils that are
overcome by the addition of normal neutrophils. Defining these is expected to lead to novel approaches to
treatment of CGD and possibly other chronic inflammatory conditions.
.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Neutrophil Nox2 controls mononuclear cell functions in inflammation; role in CGD
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批准号:10456072
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项目类别:
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财政年份:2014
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财政年份:2011
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Cell Culture Core
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财政年份:2005
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依托单位:
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批准号:7142871
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财政年份:2005
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负责人:DONNA L BRATTON
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依托单位:
Defective PS Exposure in Neutrophil Apoptosis in CGD
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批准号:6991217
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项目类别:
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资助金额:$25.91万
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财政年份:2003
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负责人:DONNA L BRATTON
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依托单位:
Defective PS Exposure in Neutrophil Apoptosis in CGD
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批准号:7154063
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项目类别:
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资助金额:$25.16万
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财政年份:2003
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Defective PS Exposure in Neutrophil Apoptosis in CGD
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财政年份:2003
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Defective PS Exposure in Neutrophil Apoptosis in CGD
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项目类别:
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资助金额:$26.53万
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财政年份:2003
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负责人:DONNA L BRATTON
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依托单位:
Membrane Phospholipid Distribution/Mediator Translocatio
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批准号:6611193
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资助金额:$22.05万
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财政年份:2002
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负责人:DONNA L BRATTON
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依托单位:
EOSINOPHILS, APOPTOSIS, AND ASTHMA
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资助金额:$24.21万
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财政年份:2002
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Membrane Phospholipid Distribution/Mediator Translocatio
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财政年份:2001
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负责人:DONNA L BRATTON
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依托单位:
TRANSBILAYER MOVEMENT OF PHOSPHOLIPIDS IN MEMBRANES
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TRANSBILAYER MOVEMENT OF PHOSPHOLIPIDS IN MEMBRANES
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依托单位:
海外基金