Role of Mononuclear Leukocytes in Immunity
单核白细胞在免疫中的作用
基本信息
- 批准号:7421090
- 负责人:
- 金额:$ 37.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1984
- 资助国家:美国
- 起止时间:1984-07-01 至 2011-04-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdhesionsAffectAlbuminsAlcoholsAmoxicillinAnimal ModelAnimalsAnti-Bacterial AgentsAntibiotic ResistanceAntibioticsAntibodiesAntigen ReceptorsAntigensApoptoticAreaAttentionAzacitidineBackBacteriaBacterial InfectionsBathingBedsBehaviorBeta-glucuronidaseBindingBiocompatible MaterialsBiological AssayBiopsyBlocking AntibodiesBloodBlood CirculationBlood VesselsBlood flowBone MarrowBrefeldin ABuffersC57BL/6 MouseC5a anaphylatoxin receptorCCL2 geneCD8B1 geneCSF1 geneCaliberCapillary Endothelial CellCardiacCartilageCathetersCell CountCell LineCell membraneCell physiologyCell surfaceCellsCentrifugationChemotactic FactorsChloratesClassCoagulation ProcessCobra VenomsCollaborationsCollagenComplementComplement 3dComplement 5aConditionConditioned Culture MediaCountCultured CellsCyclic AMP-Dependent Protein KinasesCycloheximideCytochalasin DCytolysisCytoplasmCytoplasmic GranulesCytoplasmic OrganelleDNA MethylationDailyDataDefectDepositionDepthDermalDermisDevelopmentDigestionDoctor of PhilosophyDorsalDoseE-SelectinEarEar CartilagesEffector CellElectron MicroscopyEmigrationsEndopeptidasesEndothelial CellsEndotheliumEnterotoxinsEnvironmentEnzyme-Linked Immunosorbent AssayEnzymesEquationEscherichia coliEvans blue stainEventExhibitsFc ReceptorFibrinFibrinogenFigs - dietaryFluorescenceForeign BodiesFormalinFosteringFrozen SectionsGelGene ExpressionGenerationsGlycosaminoglycansGoalsGolgi ApparatusGram-Negative BacteriaGranulocyte-Macrophage Colony-Stimulating FactorGrowthGrowth FactorHaemophilus influenzaeHandHarvestHeartHeatingHistonesHost DefenseHumanITGB2 geneIceIgEImmigrationImmuneImmune responseImmunityImmunizationImmunoglobulin GImmunoglobulinsImplantIn VitroIncubatedInfectionInfectious Diseases ResearchInflammationInflammatoryInflammatory ResponseInjection of therapeutic agentInjuryIntegrinsInterferonsInterleukin-1Interleukin-1 ReceptorsInterleukin-2Intravenous infusion proceduresInvadedKetamineKineticsKnock-outKnockout MiceKnowledgeLabelLaboratoriesLeadLearningLeftLengthLesionLettersLeukocytesLeukotriene B4LigandsLightLipidsLipopolysaccharidesLiposomesLiteratureLongevityLungLymphaticLymphocyteLysosomesMAPK14 geneMEKsMacrophage Colony-Stimulating FactorMeasuresMediatingMelanoma CellMembraneMembrane GlycoproteinsMethodsMicrobial BiofilmsMicrospheresMitogen-Activated Protein Kinase InhibitorModelingMolecularMonitorMonoclonal AntibodiesMonoclonal Antibody HuM291Mononuclear LeukocytesMontanaMorphologyMouse StrainsMuromonab-CD3MusMyelogenousMyeloid CellsNatural Killer CellsNeedlesNoduleNormal Horse SerumNumbersNumerical valueOrganellesOrganismOryctolagus cuniculusOvalbuminOvumOxidasesPD-98059PalpablePathway interactionsPeptide HydrolasesPeptidesPercollPerfusionPeroxidasePeroxidasesPhagocytesPhagocytosisPhagosomesPhasePhenotypePhosphorylationPlasmaPlasma ProteinsPlasticsPlayPositioning AttributePostdoctoral FellowPredispositionProcessProductionPropertyProsthesisProtein BiosynthesisProtein Phosphatase InhibitorProteinsProteoglycanPseudomonas aeruginosaPunch BiopsyPuncture procedurePurposeRainRateReaderReagentRecruitment ActivityRegression AnalysisReportingResearch PersonnelResidual stateResistanceResolutionRoleSB 203580SamplingSepsisSerumSignal PathwaySignal TransductionSignaling ProteinSiteSkinSkin TemperatureSonicationSourceSpeedSpleenStaining methodStainsStaphylococcus aureusSterilitySterilization for infection controlStreptococcus pneumoniaeStromal CellsStructureStudentsStudy modelsSucroseSurfaceSurgical incisionsSuspension substanceSuspensionsSwabSyringesSystemT-LymphocyteTNF geneTeflonTemperatureTenascinTestingThickThinkingThrombinTimeTissue ExtractsTissue StainsTissuesTransgenesTransgenic MiceTrichostatin ATrypsinTumor AntigensTumor-DerivedUncertaintyUniversitiesUpper armVaccinesVenousVirulence FactorsWeekWestern BlottingWild Type MouseWorkWound HealingXylazineabsorptionbactericidebaseblood flow measurementcancer cellcarboxyfluoresceincell killingcell typechemokinecollagenasecomplement C2acomplement C5bconceptculture platescytokinecytotoxicdaydemethylationdesigndesireeosinophilfluorophorehuman MAPK14 proteinhydroxy-aluminum polymerimmunogenicin vitro Assayin vitro Modelin vivoinhibitor/antagonistinsightinterestinterstitialkillingskinase inhibitorlymph flowlymph nodesmacrophagemast cellmelanomamicrobialmigrationmitogen-activated protein kinase p38monocytemonolayerneoplastic cellneutralizing antibodyneutrophilnovelnovel strategiesoral infectionpathogenperipheral bloodpressurepreventprotective effectquorum sensingreceptorresearch studyresidenceresponsesizesuccesssulfationsurface coatingsymposiumtissue culturetissue processingtumortumorigenesistwo-dimensionaluptake
项目摘要
DESCRIPTION (provided by applicant): We have used three-dimensional fibrin and collagen I gels to compare neutrophil (PMN) bactericidal activity in tissue-like environments vs. stirred suspensions and discovered that a critical PMN concentration (CNC) is required to block the growth of bacteria in fibrin and collagen gels and in stirred suspensions. The concept that a critical leukocyte concentration is required to carry out specific immune effector functions is both novel and important. It unifies a large body of literature on host defense against bacterial infections, and provides a conceptual framework for assessing quantitatively the concentration of any class or type of immune cell that must be delivered to a tissue to execute a specific function. We have derived an equation that enables us to calculate the CNC for all bacterial concentrations under all experimental conditions so far tested. Using it we found the CNC in suspension (approximately 4 x 105 PMN/ml), is almost identical to that known to predispose neutropenic humans to sepsis, while that in fibrin gels is 2.5 - 10-fold higher (e.g., 1-4 x 106PMN/ml). Using these gels we have extended our previous observation that specific matrix proteins (e.g., fibrin) and chemoattractants (e.g., fMLP) block PMN migration by showing that in the presence of fibrin, fMLP blocks PMN bactericidal activity. Moreover, we discovered that PMN genetically deficient in a2-integrins phagocytose and kill S.epidermidis as efficiently as wild-type PMN in fibrin gels. We also have discovered that contrary to conventional wisdom, PMN have the capacity to invade and kill >98% of S. epidermidis in mature (5-day old) biofilms. We seek continued support to extend these studies, and to identify mechanisms that regulate emigration of PMN and monocytes from the blood into tissues, processes central to limiting tissue damage, and to delivering sufficient PMN and monocytes to eradicate planktonic and biofilm bacteria, and cytotoxic lymphocytes to kill cancer cells. This application has three Specific Aims. Aim #1. To measure the critical concentration of monocytes for killing S. epidermidis and E. coli in fibrin and collagen I gels in vitro, and the critical concentrations of PMN and of monocytes for killing of S. epidermidis and E.coli in vivo, and to identify the mechanisms that signal cessation of entry of PMN and of monocytes into dermal sites of bacterial infection. Aim #2. To identify the immunological mechanisms that impede PMN and monocyte killing of biomaterials-associated S. epidermidis biofilms. Aim #3. To determine whether the concept of a critical leukocyte concentration also applies to the tumoricidal activities of cytotoxic lymphocytes and monocytes. In other words, must cytotoxic lymphocytes reach a critical concentration within a tumor bed to effect a reduction in tumor mass?
描述(由申请人提供):我们已经使用了三维纤维蛋白和胶原蛋白凝胶来比较组织样环境中的嗜中性粒细胞(PMN)杀菌活性与搅拌悬浮液,并发现需要临界PMN浓度(CNC)来阻止细菌在纤维蛋白和胶原蛋白凝胶中的细菌的生长。需要关键的白细胞浓度来执行特定的免疫效应功能是新颖而重要的概念。它统一了有关宿主防御细菌感染的大量文献,并提供了一个概念框架,以定量评估任何类别或类型的免疫细胞的浓度,必须将其传递到组织中以执行特定功能。我们得出了一个方程,使我们能够在迄今已测试的所有实验条件下计算所有细菌浓度的CNC。使用它,我们在悬浮液(约4 x 105 pmn/ml)中发现了CNC几乎与诱发中性粒细胞的人类已知的CNC几乎相同,而纤维蛋白凝胶中的中性粒细胞含量为2.5-10倍(例如,1-4 x 106pmn/ml)。使用这些凝胶,我们已经扩展了先前的观察结果,即特异性基质蛋白(例如纤维蛋白)和化学吸引剂(例如FMLP)通过表明在纤维蛋白存在的情况下阻止PMN迁移,FMLP阻止PMN PMN PMN杀菌活性。此外,我们发现PMN遗传缺陷在A2-促蛋白吞噬剂中,并在纤维蛋白凝胶中像野生型PMN一样有效地杀死s. epidermidis。我们还发现,与传统的智慧相反,PMN具有成熟(5天)生物膜中侵入和杀死98%表皮链球菌的能力。我们寻求继续支持这些研究,并确定调节PMN和单核细胞从血液中移民到组织的机制,对限制组织损伤的核心处理,并提供足够的PMN和单核细胞来消除浮游生物和生物生物生物生物生物细菌,以及细胞毒性淋巴细胞,以杀死癌症细胞。该应用程序具有三个具体目标。目标#1。测量单核细胞的临界浓度,用于在体外杀死纤维蛋白和胶原蛋白I凝胶中的表皮链球菌和大肠杆菌,以及在体内杀死表皮链球菌和大肠杆菌的临界PMN和单核细胞的临界浓度,并确定了细分pmn和dimocy corte corte and dimocy corte and dimocy and dimocy conters of dirmocy conters and dimocy的机制。目标#2。确定影响PMN和单核细胞相关的表皮链球菌生物膜的免疫机制。目标#3。为了确定临界白细胞浓度的概念是否也适用于细胞毒性淋巴细胞和单核细胞的肿瘤活性。换句话说,细胞毒性淋巴细胞是否必须在肿瘤床内达到临界浓度以减少肿瘤质量?
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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SAMUEL CHARLES SILVERSTEIN其他文献
SAMUEL CHARLES SILVERSTEIN的其他文献
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{{ truncateString('SAMUEL CHARLES SILVERSTEIN', 18)}}的其他基金
Summer Immunology Research Program for High School Science Teachers
高中科学教师暑期免疫学研究计划
- 批准号:
7560268 - 财政年份:2008
- 资助金额:
$ 37.88万 - 项目类别:
Summer Immunology Research Program for High School Science Teachers
高中科学教师暑期免疫学研究计划
- 批准号:
8065692 - 财政年份:2008
- 资助金额:
$ 37.88万 - 项目类别:
Summer Immunology Research Program for High School Science Teachers
高中科学教师暑期免疫学研究计划
- 批准号:
8135497 - 财政年份:2008
- 资助金额:
$ 37.88万 - 项目类别:
Summer Immunology Research Program for High School Science Teachers
高中科学教师暑期免疫学研究计划
- 批准号:
7940833 - 财政年份:2008
- 资助金额:
$ 37.88万 - 项目类别:
Health Sciences Research: Educating the Public - PHASE II
健康科学研究:教育公众 - 第二阶段
- 批准号:
7286111 - 财政年份:2003
- 资助金额:
$ 37.88万 - 项目类别:
Health Sciences Research: Educating the Public - PHASE II
健康科学研究:教育公众 - 第二阶段
- 批准号:
7175645 - 财政年份:2003
- 资助金额:
$ 37.88万 - 项目类别:
HEALTH SCIENCES RESEARCH: EDUCATION THE PUBLIC - PHASE I
健康科学研究:公众教育 - 第一阶段
- 批准号:
6936685 - 财政年份:2003
- 资助金额:
$ 37.88万 - 项目类别:
HEALTH SCIENCES RESEARCH: EDUCATION THE PUBLIC - PHASE I
健康科学研究:公众教育 - 第一阶段
- 批准号:
6803532 - 财政年份:2003
- 资助金额:
$ 37.88万 - 项目类别:
HEALTH SCIENCES RESEARCH: EDUCATION THE PUBLIC - PHASE I
健康科学研究:公众教育 - 第一阶段
- 批准号:
6671545 - 财政年份:2003
- 资助金额:
$ 37.88万 - 项目类别:
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