Milk Fat Globule-EGF Factor VIII in Sepsis and Ischemia-Reperfusion Injury
Milk Fat Globule-EGF Factor VIII in Sepsis and Ischemia-Reperfusion Injury
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DOI：
10.2119/molmed.2010.00135
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发表时间：
2011-01-01
影响因子：
5.7
通讯作者：
Wang, Ping
中科院分区：
文献类型：
--
作者：
Matsuda, Akihisa;Jacob, Asha;Wang, Ping
脓毒症和缺血再灌注（I/R）损伤是外科重症监护病房危重患者死亡的主要原因之一。这两种情况的特点是过度炎症反应，导致致命的疾病复合体，如急性肺损伤、全身炎症反应综合征和多器官功能障碍综合征。尽管对这些疾病的病理生理学的理解取得了进展，但治疗干预方面却进展甚微。这些病症的关键方面之一是凋亡细胞的积累，由于继发性坏死而没有被吞噬细胞适当清除，这些细胞有可能释放有毒和促炎内容物。据报道，除了预防细胞凋亡之外，这对脓毒症和缺血再灌注损伤有益，通过吞噬作用主动清除凋亡细胞来阻止继发性坏死的发展可能会提供一种新的治疗方法。乳脂球-EGF因子VIII（MFG-E8）主要由巨噬细胞和树突状细胞产生，是凋亡细胞的调理素，充当凋亡细胞和吞噬细胞之间的桥接蛋白。最近，我们发现实验性脓毒症和缺血再灌注损伤模型中 MFG-E8 表达降低。外源性给予 MFG-E8 可通过促进凋亡细胞的吞噬作用减轻炎症反应以及组织损伤和死亡率。在这篇综述中，我们描述了有关 MFG-E8 参与脓毒症和 I/R 损伤的病理生理学的新信息，以及外源性 MFG-E8 治疗这些疾病的治疗潜力。 (c) 2011 年范斯坦医学研究所，www.feinsteininstitute.org 在线地址：http://www.molmed.org doi: 10.2119/molmed.2010.00135
Sepsis and ischemia-reperfusion (I/R) injury are among the leading causes of death in critically ill patients at the surgical intensive care unit setting. Both conditions are marked by the excessive inflammatory response which leads to a lethal disease complex such as acute lung injury, systemic inflammatory response syndrome and multiple organ dysfunction syndrome. Despite the advances in the understanding of the pathophysiology of those conditions, very little progress has been made toward therapeutic interventions. One of the key aspects of these conditions is the accumulation of apoptotic cells that have the potential to release toxic and proinflammatory contents due to secondary necrosis without appropriate clearance by phagocytes. Along with the prevention of apoptosis, that is reported to be beneficial in sepsis and I/R injury, thwarting the development of secondary necrosis through the active removal of apoptotic cells via phagocytosis may offer a novel therapy. Milk fat globule-EGF factor VIII (MFG-E8), which is mainly produced by macrophages and dendritic cells, is an opsonin for apoptotic cells and acts as a bridging protein between apoptotic cells and phagocytes. Recently, we have shown that MFG-E8 expression is decreased in experimental sepsis and I/R injury models. Exogenous administration of MFG-E8 attenuated the inflammatory response as well as tissue injury and mortality through the promotion of phagocytosis of apoptotic cells. In this review, we describe novel information available about the involvement of MFG-E8 in the pathophysiology of sepsis and I/R injury, and the therapeutic potential of exogenous MFG-E8 treatment for those conditions. (c) 2011 The Feinstein Institute for Medical Research, www.feinsteininstitute.org Online address: http://www.molmed.org doi: 10.2119/molmed.2010.00135