In vivo imaging in mice reveals local cell dynamics and inflammation in obese adipose tissue
In vivo imaging in mice reveals local cell dynamics and inflammation in obese adipose tissue
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DOI：
10.1172/jci33328
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发表时间：
2008-02-01
影响因子：
15.9
通讯作者：
Sugiura, Seiryo
中科院分区：
文献类型：
--
作者：
Nishimura, Satoshi;Manabe, Ichiro;Sugiura, Seiryo
为了评估涉及多种细胞类型之间动态相互作用的生理和病理生理事件，实时体内分析是必要的。我们开发了一种基于共聚焦激光显微镜的技术，使我们能够以高时空分辨率分析和比较小鼠瘦和肥胖脂肪组织内的三维结构、细胞动力学和血管功能。我们发现在肥胖小鼠和高脂饮食诱导的肥胖小鼠中，肥胖内脏脂肪组织的微循环中白细胞-EC-血小板相互作用增加。这些变化表明白细胞粘附级联反应的激活，这是炎症的标志。肥胖脂肪组织中局部血小板活化表现为P-选择素表达增加和单核细胞-血小板结合物形成。我们观察到肥胖内脏脂肪组织中巨噬细胞和内皮细胞上粘附分子的表达上调，表明这些细胞之间的相互作用有助于局部激活炎症过程。此外，施用抗ICAM-1抗体使肥胖内脏脂肪中观察到的细胞动力学正常化。这种成像技术分析了肥胖脂肪组织内复杂的细胞相互作用，使我们能够表明内脏脂肪组织肥胖是一种炎症性疾病。此外，这项技术可能被证明是一个有价值的工具，以评估潜在的治疗干预措施。
To assess physiological and pathophysiological events that involve dynamic interplay between multiple cell types, real-time, in vivo analysis is necessary. We developed a technique based on confocal laser microscopy that enabled us to analyze and compare the 3-dimensional structures, cellular dynamics, and vascular function within mouse lean and obese adipose tissue in vivo with high spatiotemporal resolution. We found increased leukocyte-EC-platelet interaction in the microcirculation of obese visceral adipose tissue in ob/ob and high-fat diet-induced obese mice. These changes were indicative of activation of the leukocyte adhesion cascade, a hallmark of inflammation. Local platelet activation in obese adipose tissue was indicated by increased P-selectin expression and formation of monocyte-platelet conjugates. We observed upregulated expression of adhesion molecules on macrophages and ECs in obese visceral adipose tissue, suggesting that interactions between these cells contribute to local activation of inflammatory processes. Furthermore, administration of anti-ICAM-1 antibody normalized the cell dynamics seen in obese visceral fat. This imaging technique to analyze the complex cellular interplay within obese adipose tissue allowed us to show that visceral adipose tissue obesity is an inflammatory disease. In addition, this technique may prove to be a valuable tool to evaluate potential therapeutic interventions.