Studies On The Mechanism Of CD169+macrophages In The Marginal Zone Of The Spleen Alleviating Atherosclerosis By Removing The Activated Monocytes In The Peripheral Circulation System

Inflammation is a series of local and systemic defense responses when the body is stimulated by foreign pathogens.Under normal circumstances,inflammation can remove harmful foreign body,repair damaged tissue,and maintain their stability.However,when the inflammation is out of control,it can lead to related inflammatory diseases,such as atherosclerosis.Atherosclerosis as an inflammatory related disease,its pathogenesis is more complicated.It is generally believed that the onset of AS is due to lipid metabolism disorder,which leads to the accumulation of lipids in the intimal lesions of the blood vessels,resulting in endothelial damage,which in turn triggers inflammatory reactions and eventually forming plaques.The current clinical treatment of atherosclerosis is mainly the use of some blood lipid-lowering drugs,which can only slow down the progress of the disease and cannot be cured completely.Therefore,it is particularly important to explore the pathogenesis of atherosclerosis and establish new treatments.The monocyte in peripheral blood play a key role in the development of atherosclerosis.In the process of development of atherosclerosis,activated monocytes recruited to vascular lesion area.These activated monocytes will secrete pro-inflammatory cytokines and activate the local inflammatory response at the lesion site.Therefore,the removal of activated monocytes can inhibit the response of inflammation in the vascular lesion site and provide new ideas for the treatment of atherosclerosis.The spleen is the body’s largest immune organ,containing a large number of lymphocytes and macrophages,and has the function of filtering blood.The red pulp macrophages in the spleen can clear aging blood cells(such as red blood cells),pathogens.In recent years,a macrophage that highly expresses CD 169 protein in the marginal zone of the spleen has attracted more and more attention.CD 169,also known as siglec 1,is a member of the sialic acid-binding immunoglobulin-like lectin family.There is a lot of evidence that CD169+macrophages located in the marginal zone of the spleen plays a key role in the body’s elimination of senescent and apoptotic cells.In this study,we found that CD169+ macrophages in the marginal zone of the spleen can clear activated monocytes.The mechanism of clearing activated monocytes is.identifying the increased aminogalactose residues which are located on the surface of activated monocytes and subsequently destroy the activated cells by secreting perforin.The experimental results show that both splenectomy and knock-out of CD169+macrophages will increase the proportion of ApoE-/-mouse mononuclear cells and intensify the condition.In summary,CD169+ macrophages in the marginal zone of the spleen can relieve the occurrence and development of inflammation by eliminating activated monocytes.This finding provides a new strategy for the treatment of atherosclerosis.