New maresin conjugates in tissue regeneration pathway counters leukotriene D4-stimulated vascular responses
New maresin conjugates in tissue regeneration pathway counters leukotriene D4-stimulated vascular responses
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DOI：
10.1096/fj.201701493r
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发表时间：
2018-07-01
期刊：
影响因子：
4.8
通讯作者：
Serhan, Charles N.
中科院分区：
文献类型：
--
作者：
Chiang, Nan;Riley, Ian R.;Serhan, Charles N.
急性炎症的消退在一定程度上是由脂质介质类别从促炎二十烷类转向专门的促炎介质控制的，包括最近发现的一种新的介质途径，称为组织再生中的蛋白偶联物（MCTR），其中包括MCTR1、MCTR2和MCTR3。在这里，我们研究了每个MCTR是否会影响已知的半胱氨酸白三烯的血管作用。白三烯D-4 （LTD4, 1.5 nmol/只）引起小鼠乳突血管渗漏，MCTR1和MCTR2 （0.15 nmol/只）可使乳突血管渗漏减少75%。LTD4 （1 ~ 100 nM）诱导离体海鞘原始心脏负性肌力作用，降低心跳20 ~ 30%。每个MCTR （1-100 nM）都能阻止ltd4降低的心率。当人半胱氨酸白三烯受体-1 （CysLT1）在CHO细胞中表达时，每个MCTR （10-100 nM）显著降低ltd4启动的信号传导。为了评估CysLT1在MCTR生成中的作用，我们进行了人巨噬细胞（M phi）吞噬实验。每个MCTR （0.1 ~ 10 nM）均能刺激人M φ对活大肠杆菌的吞噬，而LTD4则不刺激人M φ的吞噬。mcr激活的吞噬作用被一种药理受体拮抗剂（MK571）显著阻断。CHO-CysLT1和人M phi s，每个MCTR竞争特异性[H-3]-LTD4结合，其亲和力明显低于LTD4。因此，每个MCTR与人类CysLT1相互作用，以药理学上拮抗血管反应并刺激生理性吞噬。m.phi s.Chiang， N., Riley， I. R., Dalli， J., Rodriguez， A. R., Spur, b.w., Serhan， C. N.组织再生途径中的新marsin偶联物对抗白三烯d -4刺激的血管反应。
Resolution of acute inflammation is governed, in part, by lipid mediator class switching from proinflammatory eicosanoids to specialized proresolving mediators, including a recently identified new pathway of mediators, termed maresin conjugates in tissue regeneration (MCTR), which includes MCTR1, MCTR2, and MCTR3. Here, we addressed whether each MCTR can impact the known vascular actions of cysteinyl leukotrienes. Leukotriene D-4 (LTD4; 1.5 nmol/mouse) initiated vascular leakage in mouse cremaster vessels, which was reduced (>75%) by MCTR1 and MCTR2 (0.15 nmol each). With isolated Ciona intestinalis (sea squirt) primordial hearts, LTD4 (1-100 nM) induced negative inotropic action and lowered heartbeats 20-30%. Each MCTR (1-100 nM) prevented LTD4-reduced heart rates. With human cysteinyl leukotriene receptor-1 (CysLT1) expressed in CHO cells, each MCTR (10-100 nM) significantly reduced LTD4-initiated signaling. To assess the contribution of CysLT1 in the proresolving actions of MCTR, we carried out human macrophage (M phi) phagocytosis. Each MCTR (0.1-10 nM) stimulated human M phi phagocytosis of live Escherichia coli, whereas LTD4 did not stimulate phagocytosis. MCTR-activated phagocytosis was significantly blocked by a pharmacologic receptor antagonist (MK571). With both CHO-CysLT1 and human M phi s, each MCTR competed for specific [H-3]-LTD4 binding with apparent lower affinity than LTD4. Thus, each MCTR functionally interacts with human CysLT1 to pharmacologically counter-regulate vascular responses and stimulate physiologic phagocytosis with M phi s.Chiang, N., Riley, I. R., Dalli, J., Rodriguez, A. R., Spur, B. W., Serhan, C. N. New maresin conjugates in tissue regeneration pathway counters leukotriene D-4-stimulated vascular responses.