Oxidized phospholipids inhibit phagocytosis and impair outcome in gram-negative sepsis in vivo
Oxidized phospholipids inhibit phagocytosis and impair outcome in gram-negative sepsis in vivo
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DOI：
10.4049/jimmunol.178.2.993
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发表时间：
2007-01-15
影响因子：
4.4
通讯作者：
van der Poll, Tom
中科院分区：
文献类型：
--
作者：
Knapp, Sylvia;Matt, Ulrich;van der Poll, Tom
在炎症过程中产生的氧化磷脂发挥抗炎作用，并防止鼠内毒素血症期间死亡。氧化的1-pamitoyl-2-arachidonoyl-sit-glycero-3-phosphorylcholine（OxPAPC）抑制LPS与LPS结合蛋白和CD 14的相互作用。在这项研究中，我们确定了OxPAPC的功能特性和潜在的干扰CD 14在腹腔脓毒症引起的大肠杆菌。OxPAPC给药使小鼠对E.大肠杆菌性腹膜炎，表现为死亡率加快和细菌生长和传播增强。CD 14（-/-）小鼠也显示死亡率和细菌生长增加，OxPAPC没有进一步损害这些动物的宿主防御。OxPAPC和CD 14缺陷损害免疫应答的机制不同：CD 14（-/-）小鼠表现出吞噬细胞向感染部位的募集显著减少，OxPAPC不影响炎性细胞的流入，但通过CD 14非依赖性机制显著降低中性粒细胞和巨噬细胞的吞噬能力。此外，OxPAPC有效抑制荧光球的摄取以及受体介导的内吞作用和液相胞饮作用。这些数据表明，氧化磷脂，如在炎症反应过程中产生的，可能有助于在革兰氏阴性脓毒症在体内通过损害专业吞噬细胞的吞噬特性的死亡率。
Oxidized phospholipids that are generated during inflammation exert anti-inflammatory properties and prevent death during murine endotoxemia. Oxidized 1-paimitoyl-2-arachidonoyi-sit-glycero-3-phosphorylcholine (OxPAPC) inhibits the interaction of LPS with LPS-binding protein and CD14. In this study, we determined the functional properties of OxPAPC and potential interference with CD14 during abdominal sepsis caused by Escherichia coli. Administration of OxPAPC rendered mice highly susceptible to E. coli peritonitis, as indicated by an accelerated mortality and enhanced bacterial outgrowth and dissemination. CD14(-/-) mice also displayed increased mortality and bacterial outgrowth and OxPAPC did not further impair host defense in these animals. The mechanisms by which OxPAPC and CD14 deficiency impaired the immune response differed: whereas CD14(-/-) mice demonstrated a strongly reduced recruitment of phagocytes to the site of the infection, OxPAPC did not influence the influx of inflammatory cells but strongly diminished the phagocytosing capacity of neutrophils and macrophages by a CD14-independent mechanism. Furthermore, OxPAPC potently inhibited uptake of fluorospheres as well as receptor-mediated endocytosis and fluid-phase pinocytosis. These data suggest that oxidized phospholipids such as produced during inflammatory reactions may contribute to mortality during Gram-negative sepsis in vivo via impairment of the phagocytic properties of professional phagocytes.