美国波士顿儿童医院Ivan Zanoni小组的最新研究发现，内源性氧化磷脂可改变细胞代谢并促进过度炎症的发生。相关论文在线发表于11月25日的《自然—免疫学》。
研究人员发现自编码氧化磷脂oxPAPC改变了遭受脂多糖感染的巨噬细胞的代谢。由脂多糖激活的细胞仅依赖于糖酵解供能，而暴露于oxPAPC的巨噬细胞也利用线粒体呼吸，并利用谷氨酰胺为Krebs循环提供原料，促进草酰乙酸在细胞质中的积累。
这种代谢产物会增强白介素-1β的产生，导致过度炎症。高胆固醇血症小鼠和人类受试者体内发生类似的代谢改变。利用药物干扰oxPAPC引起的代谢变化减少了小鼠的动脉粥样硬化斑块形成，从而揭示了损伤相关模式分子（DAMP）介导反应在生理病理条件下的重要性。
据了解，病原体相关分子模式（PAMP）具有偶合炎症基因表达与改变巨噬细胞代谢的功能，这两者都会影响随后的炎症反应。类似于它们的微生物对应物，几种自我编码的损伤相关模式分子（DAMP）诱导炎症基因的表达。然而，尚不清楚宿主体内PAMPs和DAMPs之间的这种协调是否影响到代谢的转变。
附：英文原文
Title: Endogenous oxidized phospholipids reprogram cellular metabolism and boost hyperinflammation
Author: Marco Di Gioia, Roberto Spreafico, James R. Springstead, Michael M. Mendelson, Roby Joehanes, Daniel Levy, Ivan Zanoni
Issue&Volume: 2019-11-25
Abstract: Pathogen-associated molecular patterns (PAMPs) have the capacity to couple inflammatory gene expression to changes in macrophage metabolism, both of which influence subsequent inflammatory activities. Similar to their microbial counterparts, several self-encoded damage-associated molecular patterns (DAMPs) induce inflammatory gene expression. However, whether this symmetry in host responses between PAMPs and DAMPs extends to metabolic shifts is unclear. Here, we report that the self-encoded oxidized phospholipid oxPAPC alters the metabolism of macrophages exposed to lipopolysaccharide. While cells activated by lipopolysaccharide rely exclusively on glycolysis, macrophages exposed to oxPAPC also use mitochondrial respiration, feed the Krebs cycle with glutamine, and favor the accumulation of oxaloacetate in the cytoplasm. This metabolite potentiates interleukin-1β production, resulting in hyperinflammation. Similar metabolic adaptions occur in vivo in hypercholesterolemic mice and human subjects. Drugs that interfere with oxPAPC-driven metabolic changes reduce atherosclerotic plaque formation in mice, thereby underscoring the importance of DAMP-mediated activities in pathophysiological conditions.
DOI: 10.1038/s41590-019-0539-2
Source: https://www.nature.com/articles/s41590-019-0539-2
Nature Immunology：《自然—免疫学》，创刊于2000年。隶属于施普林格·自然出版集团，最新IF：31.25
官方网址：https://www.nature.com/ni/
投稿链接：https://mts-ni.nature.com/cgi-bin/main.plex
本期文章：《自然—免疫学》：Online/在线发表
