Research Of Anti-Inflammatory Properties Of Ly6C^low Monocyte/Macrophage Subsets In Cardiac Repair Phase After Myocardial Infarction

Background and Objectives:For 70 years, recruitment, activation and inflammatory modulation of leukocytes have been studies constantly. Researchers have come to realize that inflammation is the core of regulation to prevent deterioration of cardiac failure.Monocyte/macrophage is a key modulator of inflammation after myocardial infarction, with pro- and anti-inflammatory functions. The two subsets of Ly6Chigh and Ly6Clow monocyte/macrophage can be detected in murine heart. Many studies suggested that Ly6Clow monocyte subset might be a specific effector to exert positive anti-inflammatory and pro-fibrotic functions.The study planned to build models of myocardial ischemia and reperfusion, to the extent of cellular and molecular level, further examines the post-infarction inflammatory modulation effect of Ly6Clow monocyte/macrophage subsets. By means of magnetic cell sorting and flow cytometry, we separated and identified collected cells, combined with the research status quo of IRAK-M, strived to explore the relationship between IRAK-M and Ly6Clow monocyte/macrophage subsets in their effect on inflammatory regulation. Studies above help in the elucidation of Ly6Clow monocytes’protective effects of heart, endeavor of finding specific target cells and corresponding mechanisms to facilitate myocardial healing after infarction, and presentation of novel research opportunities for therapy of improving prognosis of myocardial infarction.Methods:The study prepared single cell suspension with hearts harvested from mice on post-infarction day 7. Through magnetic cell sorting and flow cytometry, cells of interest were separated and identified. By means of double control design (see table 1 below) of MI versus non-MI and IRAK-M knock-out versus wild-type, the study explored the mechanisms of inflammatory regulation in the specific post-infarction period.Results:The study demonstrated that among IRAK-M knock-out mice, quantity of CD11b+F4/80-monocyte increases significantly in MI group than non-MI group, with no other significant difference between groups.Also, IRAK-M knock-out mice significantly decreases in the percentage of Ly6Clow cells in CD11b+F4/80+ macrophages or CD11b+F4/80-monocytes than wild-type ones in MI group, and Ly6Clow monocytes’ percentage in all CD11b+F4/80- monocytes significantly increases in MI group than non-MI group of wild-type mice.M2-type macrophage’s quantity hasn’t seen any significant difference between groups, and M2-type macrophage’s percentage in Ly6Chigh macrophages hasn’t either. However, IRAK-M knock-out mice witnessed a sigificant increase in M2-type macrophages’ percentage in Ly6Clow macrophages of MI group than non-MI group, and an increase of M2-type macrophages’ percentage in Ly6Clow macrophages took place in IRAK-M knock-out mice than wild-type ones of MI group.The study showed that of Ly6Clow macrophages or monocytes, IRAK-M group of MI mice had significantly lowered expression of IL-1RⅡ than wild-type group.Conclusion:IRAK-M modulates the phenotypes and functions of monocyte/macrophage in the environment of post-infarction inflammation, and is closely related with the quantity and effect of Ly6Clow monocyte/macrophage. Meanwhile, IRAK-M Participates in the mechanism of anti-inflammatory function of Ly6Clow monocyte/macrophage, by means of IL-1/TLRs signaling.