Enoksson Mattias, Lyberg Katarina, Möller-Westerberg Christine, Fallon Padraic G, Nilsson Gunnar, Lunderius-Andersson Carolina
Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institute, SE-171 76 Stockholm, Sweden.
J Immunol. 2011 Feb 15;186(4):2523-8. doi: 10.4049/jimmunol.1003383. Epub 2011 Jan 14.
In response to cell injury, caused, for example, by trauma, several processes must be initiated simultaneously to achieve an acute inflammatory response designed to prevent sustained tissue damage and infection and to restore and maintain tissue homeostasis. Detecting cell injury is facilitated by the fact that damaged cells release intracellular molecules not normally present in the extracellular space. However, potential underlying mechanisms for the recognition of endogenous danger signals released upon cell injury have yet to be elucidated. In this study, we demonstrate that mast cells, potent promoters of acute inflammation, play a key role in responding to cell injury by recognizing IL-33 released from necrotic structural cells. In an in vitro model of cell injury, this recognition was shown to involve the T1/ST2 receptor and result in the secretion of proinflammatory leukotrienes and cytokines by mouse mast cells. Remarkably, of all of the components released upon necrosis, our results show that IL-33 alone is a key component responsible for initiating proinflammatory responses in mast cells reacting to cell injury. Our findings identify IL-33 as a key danger signal released by necrotic structural cells capable of activating mast cells, thus providing novel insights concerning the role of mast cells as sensors of cell injury.
针对例如由创伤引起的细胞损伤，必须同时启动几个过程，以实现旨在防止持续组织损伤和感染并恢复和维持组织稳态的急性炎症反应。受损细胞释放细胞外空间中通常不存在的细胞内分子，这有助于检测细胞损伤。然而，细胞损伤时释放的内源性危险信号的潜在识别机制尚未阐明。在本研究中，我们证明肥大细胞作为急性炎症的有力促进者，通过识别坏死结构细胞释放的白细胞介素-33（IL-33）在应对细胞损伤中起关键作用。在细胞损伤的体外模型中，这种识别被证明涉及T1/ST2受体，并导致小鼠肥大细胞分泌促炎白三烯和细胞因子。值得注意的是，在坏死时释放的所有成分中，我们的结果表明，单独的IL-33是在对细胞损伤作出反应的肥大细胞中引发促炎反应的关键成分。我们的发现确定IL-33是坏死结构细胞释放的能够激活肥大细胞的关键危险信号，从而为肥大细胞作为细胞损伤传感器的作用提供了新的见解。
