Schwab Jan M, Chiang Nan, Arita Makoto, Serhan Charles N
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Nature. 2007 Jun 14;447(7146):869-74. doi: 10.1038/nature05877.
Resolution of acute inflammation is an active process essential for appropriate host responses, tissue protection and the return to homeostasis. During resolution, specific omega-3 polyunsaturated fatty-acid-derived mediators are generated within resolving exudates, including resolvin E1 (RvE1) and protectin D1 (PD1). It is thus important to pinpoint specific actions of RvE1 and PD1 in regulating tissue resolution. Here we report that RvE1 and PD1 in nanogram quantities promote phagocyte removal during acute inflammation by regulating leukocyte infiltration, increasing macrophage ingestion of apoptotic polymorphonuclear neutrophils in vivo and in vitro, and enhancing the appearance of phagocytes carrying engulfed zymosan in lymph nodes and spleen. In this tissue terrain, inhibition of either cyclooxygenase or lipoxygenases--pivotal enzymes in the temporal generation of both pro-inflammatory and pro-resolving mediators--caused a 'resolution deficit' that was rescued by RvE1, PD1 or aspirin-triggered lipoxin A4 analogue. Also, new resolution routes were identified that involve phagocytes traversing perinodal adipose tissues and non-apoptotic polymorphonuclear neutrophils carrying engulfed zymosan to lymph nodes. Together, these results identify new active components for postexudate resolution traffic, and demonstrate that RvE1 and PD1 are potent agonists for resolution of inflamed tissues.
急性炎症的消退是一个活跃过程，对于适当的宿主反应、组织保护以及恢复内环境稳态至关重要。在消退过程中，在消退性渗出物中会产生特定的ω-3多不饱和脂肪酸衍生介质，包括消退素E1（RvE1）和保护素D1（PD1）。因此，明确RvE1和PD1在调节组织消退中的具体作用很重要。在此我们报告，纳克量的RvE1和PD1通过调节白细胞浸润、在体内和体外增加巨噬细胞对凋亡多形核中性粒细胞的摄取以及增强在淋巴结和脾脏中携带吞噬的酵母聚糖的吞噬细胞的出现，促进急性炎症期间吞噬细胞的清除。在这种组织环境中，抑制环氧化酶或脂氧合酶（这两种酶在促炎和促消退介质的生成过程中起关键作用）会导致“消退缺陷”，而RvE1、PD1或阿司匹林触发的脂氧素A4类似物可挽救这种缺陷。此外，还确定了新的消退途径，包括吞噬细胞穿过淋巴结周围脂肪组织以及携带吞噬的酵母聚糖的非凋亡多形核中性粒细胞进入淋巴结。总之，这些结果确定了渗出物后消退过程中的新活性成分，并证明RvE1和PD1是炎症组织消退的有效激动剂。
