Abstract:Aim To identify the role of low density lipoprotein receptor (LDLR) on the proliferation and differentiation of CD11b＋ myeloid subsets, particularly CD11b＋Gr-1＋ immature myeloid cells with LDLR deficiency mice; To explore the mechanism of abnormal immune cell reaction in the pathogenesis of atherosclerosis. Methods 6-8 weeks old LDLR－/－ mice and control wild type (WT) C57 mice were fed with normal diet and high-fat diet for 12 weeks. Flow cytometry was used to analyze the subsets of immune cells in peripheral blood, spleen and bone marrow, especially the expressions of CD11b＋Gr-1＋ myeloid immune cell, CD11b＋Ly6C＋ mononuclear macrophage and CD11b＋CD11c＋ dendritic cell. Simultaneously the expression of Lin－Sca-1－CD34＋cKit＋ common myeloid progenitor (CMP) was detected in LDLR－/－ mouse bone marrow. Using 125I marker anti-CD11b as a molecular probe, inflammatory microenvironment of LDLR－/－ mice aortic atherosclerotic plaque was monitored noninvasively in vivo. Results (1)Under the condition of normal diet and high-fat diet, LDLR deficiency markedly enhanced the expressions CD11b＋ and CD11b＋Gr-1＋ myeloid cells in peripheral blood and spleen of LDLR－/－ mice. (2)The expression of CD11b＋Ly6C＋ mononuclear macrophages increased in peripheral blood and liver of LDLR－/－ mice; The expression of CD11b＋CD11c＋ dendritic cells increased in the spleen of LDLR－/－ mice. (3)Under normal diet, the percentage of CMP was increased in LDLR－/－ mice bone marrow compared with WT mice, but decreased under high-fat diet. (4)Using CD11b as the molecular target of inflammation, SPECT/CT could be used to monitor the atherosclerotic plaque of LDLR－/－ mouse in real time. Conclusion LDLR deficiency significantly increases the proliferation and mobilization of CD11b＋Gr-1＋ myeloid immune cells, and promotes the differentiation of mononuclear macrophage and maturation of dendritic cell in LDLR－/－ mice. With CD11b＋ myeloid cells as a target, the inflammatory microenvironment of atherosclerotic plaques can be monitored in vivo.
