Splenic leukocytes define the resolution of inflammation in heart failure.
Splenic leukocytes define the resolution of inflammation in heart failure.
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DOI：
10.1126/scisignal.aao1818
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发表时间：
2018-03-06
影响因子：
7.3
通讯作者：
Ingle KA
中科院分区：
文献类型：
--
作者：
Halade GV;Norris PC;Kain V;Serhan CN;Ingle KA
炎症促进心肌梗死的愈合，但如果未解决，则会导致心力衰竭。为了定义炎症和消退反应，我们量化了心肌梗死后梗死左心室和脾脏中的白细胞运输和专门的促消退介质（SPMs），目的是区分炎症和消退。我们的数据表明，脾脏不仅作为白细胞库，但也是在小鼠冠状动脉结扎后SPM活跃产生的网站。心肌梗死前，SPMs在脾脏比在左心室更丰富。在冠脉结扎后第1天，脾脏白细胞减少，这一现象与梗死左心室中白细胞数量增加以及同一部位SPM生成增加有关，特别是消退素、maresin、脂氧素和保护素。此外，心肌梗死的左心室表现出编码脂氧合酶的基因表达增加，这些酶产生的SPM产量增加。我们发现巨噬细胞是SPM产生所必需的。心肌梗死前脾脏中SPM的丰度和心肌梗死后24小时内梗死左心室中SPM浓度的增加与炎症的消退在时间上相关。因此，急性炎症反应与心肌梗死后的主动消退期相一致，这表明有必要进一步研究心力衰竭中巨噬细胞源性SPM。白细胞向心脏移动，可能是心肌梗死后炎症消退脂质的来源。心肌梗死后，白细胞从脾脏向缺血心脏移动，并产生炎症缓解脂质。虽然白细胞可以引发炎症，加剧心脏病发作，他们也可以产生生物活性的解决介质，抑制炎症。Halade等人追踪了白细胞群，并测量了减轻冠状动脉结扎小鼠炎症的促消退生物活性介质的浓度，冠状动脉结扎是一种诱导心肌梗死进展为不可逆心力衰竭的实验方法。他们的分析表明，白细胞从脾脏动员到梗死的心脏，产生促消退介质，巨噬细胞的特异性消耗与促消退介质生物合成的缺乏有关。因此，通常在心脏病发作后防止免疫细胞浸润也可能通过允许炎症继续减轻来延迟愈合和恢复。
Inflammation promotes healing in myocardial infarction but if unresolved, it leads to heart failure. To define the inflammatory and resolving responses, we quantified leukocyte trafficking and specialized proresolving mediators (SPMs) in the infarcted left ventricle and spleen after myocardial infarction, with the goal of distinguishing inflammation from its resolution. Our data suggest that the spleen not only served as a leukocyte reservoir but also was the site where SPMs were actively generated after coronary ligation in mice. Before myocardial infarction, SPMs were more abundant in the spleen than in the left ventricle. At day 1 after coronary ligation, the spleen was depleted of leukocytes, a phenomenon that was associated with greater numbers of leukocytes in the infarcted left ventricle and increased generation of SPMs at the same site, particularly resolvins, maresin, lipoxins, and protectin. In addition, the infarcted left ventricle showed increased expression of genes encoding lipoxygenases and enhanced production of SPMs generated by these enzymes. We found that macrophages were necessary for SPM generation. The abundance of SPMs in the spleen before myocardial infarction and increased SPM concentrations in the infarcted left ventricle within 24 hours after myocardial infarction were temporally correlated with the resolution of inflammation. Thus, the acute inflammatory response coincided with the active resolving phase in post-myocardial infarction and suggests that further investigation into macrophage-derived SPMs in heart failure is warranted. Leukocytes mobilize to the heart and may be the source of inflammation-resolving lipids after myocardial infarction. Leukocytes mobilize from the spleen to the ischemic heart and generate inflammation-resolving lipids after myocardial infarction. Although leukocytes can trigger inflammation that aggravates a heart attack, they can also produce bioactive resolving mediators that suppress inflammation. Halade et al. tracked leukocyte populations and measured the concentrations of pro-resolving bioactive mediators that attenuate inflammation in mice subjected to coronary ligation, an experimental method of inducing myocardial infarction that progresses to irreversible heart failure. Their analysis suggests that leukocytes were mobilized from the spleen to the infarcted heart to produce pro-resolving mediators and specific depletion of macrophages was associated with the lack of pro-resolving mediators biosynthesis. Thus, generally preventing immune cell infiltration after a heart attack may also delay healing and recovery by allowing inflammation to continue abated.
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影响因子：
20.1
作者：
Ismahil MA;Hamid T;Bansal SS;Patel B;Kingery JR;Prabhu SD
通讯作者：
Prabhu SD
DOI：
10.1084/jem.20132011
发表时间：
2014-07-28
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Endo J;Sano M;Isobe Y;Fukuda K;Kang JX;Arai H;Arita M
通讯作者：
Arita M
影响因子：
20.1
作者：
Frangogiannis NG
通讯作者：
Frangogiannis NG
影响因子：
20.1
作者：
Bauer M;Cheng S;Jain M;Ngoy S;Theodoropoulos C;Trujillo A;Lin FC;Liao R
通讯作者：
Liao R
DOI：
10.4049/jimmunol.0903282
发表时间：
2010-05-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Halade GV;Rahman MM;Bhattacharya A;Barnes JL;Chandrasekar B;Fernandes G
通讯作者：
Fernandes G