Intravital microscopy imaging of macrophage localization to immunogenic particles and co-localized tissue oxygen saturation
Intravital microscopy imaging of macrophage localization to immunogenic particles and co-localized tissue oxygen saturation
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DOI：
10.1016/j.actbio.2010.03.006
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发表时间：
2010-09-01
影响因子：
9.7
通讯作者：
Sorg, Brian S.
中科院分区：
文献类型：
--
作者：
Choe, Se-woon;Acharya, Abhinav P.;Sorg, Brian S.
设计良好的基于生物材料聚合物颗粒的疫苗将最佳地促进免疫细胞抗原呈递行为，同时最小化对颗粒和包封的药物或佐剂的不良炎症反应。在基于颗粒的疫苗的设计中，考虑免疫应答对接种部位组织的可能有害影响是重要的。活体显微镜与啮齿动物背部皮肤窗口室，使在体内连续观察在同一动物，和这种模型已被用来研究血管生成和巨噬细胞对植入的生物材料的反应也可能是有用的颗粒为基础的疫苗的发展。据我们所知，目前还没有活体显微镜记录实时免疫细胞定位和潜在有害的共定位组织效应的报告。在这项原理验证研究中，我们使用荧光和光谱成像小鼠窗口室活体显微镜来测量巨噬细胞定位和共定位组织微血管血红蛋白饱和度的变化，以响应来自负载有脂多糖（LPS）的聚合物颗粒的免疫原性刺激，作为模型疫苗/佐剂系统。我们观察到更大和更快的巨噬细胞定位到更强的炎症刺激，从LPS负载的颗粒剂量，减少微血管氧合的趋势，增加巨噬细胞积累，并在极端情况下，完全微血管塌陷伴随组织坏死。我们的技术可能是有用的优化设计的颗粒为基础的疫苗，并可能会让洞察到使用血红蛋白饱和度作为组织炎症的生物标志物的颗粒为基础的疫苗的临床研究。(C)2010 Acta Materialia Inc.由爱思唯尔有限公司出版。保留所有权利。
Well-designed biomaterial polymer particle-based vaccines will optimally promote immune cell antigen-presenting behavior while minimizing adverse inflammatory responses to the particles and encapsulated drugs or adjuvants. It is important in the design of particle-based vaccines to consider possible harmful effects of immune response on tissue at the vaccination site. Intravital microscopy with rodent dorsal skin window chambers enables in vivo serial observations in the same animal, and such models which have been used to study angiogenesis and macrophage response to implanted biomaterials may also be useful for the development of particle-based vaccines. To our knowledge there have been no reports where intravital microscopy has documented real-time immune cell localization and potentially harmful co-localized tissue effects. In this proof-of-principle study we used fluorescence and spectral imaging intravital microscopy of mouse window chambers to measure macrophage localization and co-localized tissue microvessel hemoglobin saturation changes in response to an immunogenic stimulus from polymer particles loaded with lipopolysaccharide (LPS) serving as a model vaccine/adjuvant system. We observed greater and faster macrophage localization to stronger inflammatory stimuli from LPS-loaded particle doses, a trend of decreased microvessel oxygenation with increased macrophage accumulation and, in an extreme case, complete microvessel collapse accompanied by tissue necrosis. Our technique may be useful for optimizing design of particle-based vaccines and may give insight into the use of hemoglobin saturation as a biomarker of tissue inflammation for clinical investigations of particle-based vaccines. (C) 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.