Research ArticleImmunology

Splenic leukocytes define the resolution of inflammation in heart failure

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Sci. Signal.  06 Mar 2018:
Vol. 11, Issue 520, eaao1818
DOI: 10.1126/scisignal.aao1818

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Calming the heart after a heart attack

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 proresolving 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 proresolving mediators and specific depletion of macrophages was associated with the biosynthesis of proresolving mediators. Thus, generally preventing immune cell infiltration after a heart attack may also delay healing and recovery by allowing inflammation to continue abated.


Inflammation promotes healing in myocardial infarction but, if unresolved, 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.

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