Macrophages are immune-sensing "big eater" phagocytic cells responsible for an innate, adaptive, and regenerative response. After myocardial infarction, macrophages predominantly clear the deceased cardiomyocyte apoptotic or necrotic neutrophils to develop a regenerative and reparative program with the activation of the lipoxygenase-mediated maresin (MaR) metabolome at the site of ischemic injury. The specialized proresolving molecule and macrophage mediator in resolving inflammation, MaR-1, produced by human macrophages, has potent defining effects that limit polymorphonuclear neutrophil infiltration, enhance uptake of apoptotic PMNs, regulate inflammation resolution and tissue regeneration, and reduce pain. In addition to proresolving and anti-inflammatory actions, MaR-1 displays potent tissue regenerative effects in stroke and is an antinociceptive. Macrophages actively participate in the biosynthesis of bioactive MaR-2, which exhibits anti-inflammatory, proresolving, and atherosclerotic effects. A new class of macrophage-derived molecules, MaR conjugates in tissue regeneration, is identified that regulates phagocytosis and the repair and regeneration of damaged tissue. The presented review provides a current summary of the effect of MaR in resolution pathophysiology, with relevance to a cardiac repair program.-Jadapalli, J. K., Halade, G. V. Unified nexus of macrophages and maresins in cardiac reparative mechanisms.
Keywords: inflammation; myocardial infarction; myocardium regeneration; myocardium repair; resolution of inflammation.