Anti-MIF antibody treatment effectively attenuated splenic monocyte mobilization and inflammatory responses post-myocardial infarction, protecting the heart from severe ischemic injury.
Does anti-MIF antibody treatment or genetic MIF deletion reduce post-infarct inflammation and improve cardiac remodeling in a mouse model of myocardial infarction?
Pharmacological inhibition of macrophage migration inhibitory factor (MIF) attenuates post-infarct inflammation and prevents adverse cardiac remodeling in mice, highlighting a potential therapeutic target for myocardial infarction.
• Global MIF promotes inflammatory responses and splenic monocytes mobilization. • MIF through CCR2 and CXCR4 promotes PBMCs migration and infiltration. • MIF through AT-1R promotes the splenic monocyte mobilization. • Inflammatory-cell-derived MIF produced pro-inflammatory effects. • Cardiac-derived MIF exerted anti-inflammatory influence and facilitated healing. • Anti-MIF antibodies treatment diminished inflammation and prevented adverse cardiac remodeling. Recent studies indicate that macrophage migration inhibitory factor (MIF) has a dual role in myocardial infarction (MI), with different cellular sources of MIF influencing inflammation and healing differentially. To investigate the role and underlying mechanism of MIF in MI and interventional efficacy targeting MIF. Wild-type (WT), global MIF gene knockout (KO) and chimeric mice were subjected to coronary artery occlusion. The inflammatory responses and healing processes following MI were studied in both in vivo and in vitro settings. Furthermore, the therapeutic potential of pharmacological MIF inhibition to improve the prognosis of MI was explored. Globally, MIF enhanced systemic and local inflammatory responses, as well as splenic monocyte mobilization, in mice with MI. MIF promoted monocyte migration through CCR2 and CXCR4 in peripheral blood mononuclear cells (PBMCs) and the infarcted myocardium. Additionally, MIF augmented angiotensin Ⅱ type 1 receptor (AT-1R) expression and interacted with AT-1R to promote the splenic monocyte mobilization following acute MI. MIF derived from bone marrow cells (KO WT mice) had stronger systemic and local inflammatory responses and augmented mobilization of splenic monocytes. In contrast, deficiency of MIF in leukocytes (WT KO mice) increased Ly-6C low monocyte accumulation, M2 macrophage infiltration, and degree of myocardial fibrosis in infarcted myocardium. In vitro , MIF derived from ischemic heart enhanced M2 but impaired M1 macrophage marker expression in PBMCs. Anti-MIF treatment effectively attenuated splenic monocyte mobilization and both systemic and regional inflammatory responses post-MI without affecting the healing process, thereby improving the long-term prognosis. Deletion of global and inflammatory-cell-derived MIF diminished inflammation following MI by inhibiting monocyte mobilization and downregulating pro-inflammatory mediators, while cardiac-derived MIF exerted anti-inflammatory influence and facilitated healing. Furthermore, MIF antibody therapy protected the heart from severe ischemic injury and improved long-term prognosis.
Zhao et al. (Fri,) conducted a other in Myocardial infarction. Anti-MIF polyclonal antibody vs. Non-specific isotype control rabbit IgG was evaluated on Systemic and local inflammatory responses and splenic monocyte mobilization. Anti-MIF antibody treatment effectively attenuated splenic monocyte mobilization and inflammatory responses post-myocardial infarction, protecting the heart from severe ischemic injury.