Leukocyte Trafficking: From Flow Blood to Tissue

白细胞贩运：从血液流向组织

• 批准号: 7274773
• 负责人: LARRY V. MC INTIRE
• 金额: $ 90.62万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-29 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7274773
• 关键词: Acute; Adhesions; Adhesives; Agonist; Behavior; Biocompatible Materials; Biological; Biology; Biomechanics; Biomedical Engineering; Blood Vessels; Blood flow; Cell Adhesion Molecules; Characteristics; Clinical; Complex; Condition; Databases; Endothelial Cells; Ensure; Event; Experimental Models; Extracellular Matrix; Extravasation; Functional disorder; Goals; Immigration; In Vitro; Inflammation; Inflammatory; Interdisciplinary Study; Lead; Leukocyte Trafficking; Leukocytes; Liquid substance; Medicine; Modeling; Molecular; Movement; Neutrophil Activation; Permeability; Physiology; Process; Proteolysis; Research; Retinal Cone; Rice; Signal Transduction; Site; Stimulus; Structure; Surface; System; Testing; Tissues; Universities; Vascular Permeabilities; cellular engineering; college; in vivo; intravital microscopy; migration; mimetics; mouse model; neonate; neutrophil; novel; receptor; response; success

DESCRIPTION (provided by applicant): This Bioengineering Research Partnership proposal combines expertise from the Bioengineering Department at Rice University and the Section of Leukocyte Biology from Baylor College of Medicine to examine the detailed sequential processes involved in movement of leukocytes from flowing blood to migration in tissues. A systems approach is presented, with the goal of identifying the crucial molecular mechanisms involved at each step and then integration of the steps as would occur in vivo. Both in vitro and in vivo (principally mice) models will be employed - the former to test specific molecular hypotheses and the latter to ensure that mechanisms identified in vitro are of importance in the actual in vivo setting. Three specific aims are proposed Specific Aim 1 The study of the effects of fluid shear and the interactions of leukocytes and endothelial cells on adherent leukocytes. This aim will use cone-plate viscometry and parallel plate flow systems to investigate the influence of shear on secretory functions and phenotypic changes in adherent neutrophils Specific Aim 2. The study of the interactions of leukocytes and endothelial cells under shear conditions and the effects on vascular permeability. This aim will use both in vitro and in vivo experimental models to investigate the sites of neutrophil adhesion and transmigration, and changes in endothelial and vascular permeability Specific Aim 3. The study of the mechanisms of leukocyte migration through extracellular matrix, and the phenotypic changes induced by the processes required for transendothelial migration. This aim will utilize a synthetic mimetic of extracellular matrix to investigate the contributions of proteolysis, adhesion and haptotaxis in vitro, and intravital microscopy to investigate migration through extracellular matrix in vivo. Basic bioengineering expertise is crucial for the success of each Specific Aim and for the integration of aims - involving aspects of biomechanics, transport phenomena, complex biological systems, cellular engineering and biomaterials. We believe the results of these interdisciplinary studies, combining quantitative bioengineering models, novel biomaterials, basic leukocyte biology and fundamental vascular biology will lead to significant advances in our understanding of leukocyte trafficking, with important implications in both normal physiology and various pathological states.

描述（由申请人提供）：该生物工程研究合作伙伴计划结合了莱斯大学生物工程系和贝勒医学院白细胞生物学科的专业知识，以检查白细胞从流动血液到组织迁移的详细顺序过程。提出了一种系统方法，其目标是确定每个步骤中涉及的关键分子机制，然后将这些步骤整合为体内发生的步骤。 将采用体外和体内（主要是小鼠）模型-前者用于测试特定的分子假设，后者用于确保体外鉴定的机制在实际体内环境中具有重要意义。具体目的1研究流体剪切力对粘附白细胞的影响以及白细胞与内皮细胞的相互作用。本研究将使用锥板粘度计和平行板流动系统来研究剪切对粘附中性粒细胞特异性目的2的分泌功能和表型变化的影响。在剪切条件下研究白细胞和内皮细胞的相互作用及其对血管通透性的影响。该目标将使用体外和体内实验模型来研究中性粒细胞粘附和迁移的位点，以及内皮和血管通透性的变化。研究白细胞通过细胞外基质迁移的机制，以及由跨内皮迁移所需过程诱导的表型变化的学科。这一目标将利用细胞外基质的合成模拟物来研究蛋白水解，粘附和haptotaxis在体外的贡献，和活体显微镜研究迁移通过细胞外基质在体内。基本的生物工程专业知识对于每个特定目标的成功和目标的整合至关重要-涉及生物力学，运输现象，复杂的生物系统，细胞工程和生物材料等方面。我们相信这些跨学科研究的结果，结合定量生物工程模型，新型生物材料，基础白细胞生物学和基础血管生物学，将导致我们对白细胞运输的理解取得重大进展，在正常生理和各种病理状态下具有重要意义。

项目成果

Myoendothelial gap junction frequency does not account for sex differences in EDHF responses in rat MCA.

肌内皮间隙连接频率不能解释大鼠 MCA EDHF 反应的性别差异。

• DOI: 10.1016/j.mvr.2007.03.003
• 发表时间: 2007
• 期刊: Microvascular research
• 影响因子: 3.1
• 作者: Sokoya,ElkeM;Burns,AlanR;Marrelli,SeanP;Chen,Jie
• 通讯作者: Chen,Jie

Bioactive hydrogel substrates: probing leukocyte receptor-ligand interactions in parallel plate flow chamber studies.

生物活性水凝胶底物：在平行板流室研究中探测白细胞受体 - 配体相互作用。

• DOI: 10.1007/s10439-006-9173-x
• 发表时间: 2006-11
• 期刊: ANNALS OF BIOMEDICAL ENGINEERING
• 影响因子: 3.8
• 作者: Taite, Lakeshia J.;Rowland, Maude L.;Ruffino, Katie A.;Smith, Bryan R. E.;Lawrence, Michael B.;West, Jennifer L.
• 通讯作者: West, Jennifer L.