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Vascular endothelial cells and macrophages coordinate neutrophil trafficking in inflammation

血管内皮细胞和巨噬细胞协调炎症中的中性粒细胞运输

基本信息

批准号：
10632141
负责人：
Ronen Sumagin
金额：
$ 38.75万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-04 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10632141
关键词：
Actins Acute Adhesions Adhesives Binding Blood Vessels CD31 Antigens Cell Adhesion Molecules Cell physiology Cells Cues Cytoskeletal Modeling Cytoskeleton Data Effector Cell Endothelial Cells Endothelium Event Goals Homeostasis Host Defense Hot Spot Immune Immune response Infiltration Inflammation Inflammatory Bowel Diseases Injury Intercellular Junctions Knockout Mice Ligands Ligation Macrophage Mediating MicroRNAs Modeling Molecular Molecular Target Mucositis Mucous Membrane Mus Neutrophil Infiltration Pathologic Physiological Process Regulation Reporter Resolution Signal Transduction Site Tissues Vascular Endothelial Cell Work cadherin 5 cytokine extracellular vesicles healing improved interest interstitial intravital microscopy migration molecular imaging neutrophil novel novel therapeutic intervention receptor recruit response tissue injury trafficking two-photon vesicular release

项目摘要

Title: Vascular endothelial cells and macrophages coordinate neutrophil trafficking in inflammation Abstract Many pathological conditions occur due to or involve deregulated immune cell trafficking and/or effector function. In particular, tissue accumulation of innate immune cells termed neutrophils (PMN) while essential for host defense and tissue homeostasis, often leads to exacerbated inflammation. Crossing of the endothelial barrier is the first critical regulatory step in tissue PMN effector function. Many receptor-ligand interactions involved this cascade have been well-defined, however, cues that initiate and terminate this process are less understood. Our data identified a novel synergistic function of endothelial cells (ECs) and interstitial macrophages (Mϕs) in regulating this importnant process in inflamed mucosa. We found that EC-specific cues attract Mϕs to the vessel wall, and that Mϕs extend cellular protrusions to form transient junctions with ECs. Through these binding interactions and the release of extracellular vesicles (EVs), which transport regulatory microRNAs, Mϕs can transduce the necessary signaling events in ECs to preferentially accommodate PMN TEM. Thus, the overall goal of this proposal is to define mechanisms and signaling events that regulate interstitial Mϕ recruitment and contact with the vessel wall to locally prime EC responses and guide PMN TEM in inflamed mucosa. We will utilize state-of-the-art 2-photon intravital microscopy (2pIVM), relevant reporter and KO mice in models of mucosal inflammation to 1. Determine how interstitial Mϕs are recruited to interact with vascular ECs in inflamed tissue. 2. Define mechanisms by which Mϕs prime vascular ECs to form PMN TEM hot spots. 3. Determine the extent to which Mϕ-priming of vascular ECs (hot spot formation) is required for PMN TEM and resolution of tissue inflammation. Our studies will define new mechanisms of PMN trafficking, and likely identify new molecular targets to improve resolution of inflammation.

题目：血管内皮细胞和巨噬细胞在炎症中协调中性粒细胞运输