Inflammation without Vascular Leakage Science Fiction No Longer?
Inflammation without Vascular Leakage Science Fiction No Longer?
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DOI：
10.1164/rccm.201905-1011cp
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发表时间：
2019-12-15
影响因子：
24.7
通讯作者：
Lee, Warren L.
中科院分区：
文献类型：
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作者：
Filewod, Niall C.;Lee, Warren L.
血管渗漏是感染性休克和急性呼吸窘迫综合征等危重疾病的特征。它导致低血压和组织水肿，并导致器官功能障碍。长期以来，人们一直认为血管通透性增加是炎症的自然结果;特别是，许多临床医生认为，它不可避免地发生在白细胞募集到感染部位期间。事实上，大量的研究表明，血管渗漏和白细胞迁移不一定同时发生在血管中。支持这些过程的分子机制允许白细胞退出循环而不增加血管通透性开始被阐明，并建立血管渗漏作为一个可行的治疗目标。几项临床前研究表明，可以在不损害细胞因子产生、白细胞募集和病原体清除的情况下减少血管渗漏。认识到白细胞运输和血管通透性可以分别调节，应该刺激开发减少血管渗漏和组织水肿而不损害免疫反应的治疗方法。
Vascular leakage is a characteristic of critical illnesses such as septic shock and acute respiratory distress syndrome. It results in hypotension and tissue edema and contributes to organ dysfunction. It has long been taught that increased vascular permeability is a natural consequence of inflammation; in particular, many clinicians believe that it occurs inevitably during leukocyte recruitment to a site of infection. In fact, abundant research now indicates that vascular leakage and leukocyte emigration do not necessarily occur together in a blood vessel. The molecular mechanisms underpinning these processes-allowing leukocytes to exit the circulation without increasing vascular permeability-are starting to be elucidated and establish vascular leakage as a viable therapeutic target. Several preclinical studies indicate that vascular leakage can be reduced without impairing cytokine production, leukocyte recruitment, and pathogen clearance. The realization that leukocyte traffic and vascular permeability can be regulated separately should spur development of therapies that decrease vascular leakage and tissue edema without compromising the immune response.