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1737 Effects of MiR-451a on the Phagocytosis and Polarization of Macrophages

Program: Oral and Poster Abstracts
Session: 201. Granulocytes, Monocytes, and Macrophages: Poster II
Hematology Disease Topics & Pathways:
Biological Processes, immune cells, Cell Lineage, immune mechanism, microenvironment
Sunday, December 6, 2020, 7:00 AM-3:30 PM

Xiaoli Liu, postgraduate*, Dongyue Zhang, postgraduate*, Hao Wang, Ph.D. candidate*, Qian Ren*, Lina Wang, Ph.D*, Weiping Yuan, PhD, MD and Guoguang Zheng, PhD*

State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China

Macrophages are important member in tissue microenvironments and play diverse physiologic and pathologic roles. Leukemia associated macrophages (LAM) are a kind of specifically activated macrophages in leukemia microenvironment, which are different from M1, M2 and TAMs. We have reported the heterogeneities in gene expression profiles of LAMs. However, MicroRNA expression profiles of LAMs and regulatory mechanism are still unknown. Here, a MLL-AF9 induced mouse acute myeloid leukemia (AML) model was used, and LAMs in the spleen and bone marrow were sorted for microRNA sequencing. The microRNA expression profiles of LAMs in bone marrow and spleen in AML mice were different from macrophages from control mice. Based on the volcano plot, more than 100 microRNAs were differentially expressed in LAMs compared with macrophages in control mice. Next, five differentially expressed microRNAs were selected and verified by qRT-PCR in LAMs from spleen. The results showed that miR-451a and miR-155-5p in spleen LAMs were significantly upregulated in LAMs from spleen. Overexpression of miR-451a altered the morphology of macrophages, enhanced the phagocytic ability of macrophages, and promotes the expression of macrophage differentiation marker CD11b. Furthermore, overexpression of miR-451a had little effect on M0 macrophages, but increased the proliferation capacity of macrophages upon stimulation toward M1 or M2 phenotype. MiR-451a overexpressed-macrophages had higher level of iNOS when stimulated with LPS or IL-4 whereas there was no difference in the expression of IL-1β, IL-6, CD206 and Arg-1 between MiR-451a overexpressed-macrophages and control macrophage. Therefore, our data revealed the characteristics of the microRNA expression profile of LAMs for the first time, and verified the effect of miR-451a on macrophage in vitro.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH