CD100 Effects in Macrophages and Its Roles in Atherosclerosis

Abstract

CD100 or Sema4D is a protein from the semaphorin family with important roles in the vascular, nervous and immune systems. It may be found as a membrane bound dimer or as a soluble molecule originated by proteolytic cleavage. Produced by the majority of hematopoietic cells including B and T lymphocytes, natural killer and myeloid cells, as well as endothelial cells, CD100 exerts its actions by binding to different receptors depending on the cell type and on the organism. Cell-to-cell adhesion, angiogenesis, phagocytosis, T cell priming, and antibody production are examples of the many functions of this molecule. Of note, high CD100 serum levels has been found in inflammatory as well as in infectious diseases, but the roles of the protein in the pathogenesis of these diseases has still to be clarified. Macrophages are highly heterogeneous cells present in almost all tissues, which may change their functions in response to microenvironmental conditions. They are key players in the innate and adaptive immune responses and have decisive roles in sterile conditions but also in several diseases such as atherosclerosis, autoimmunity, tumorigenesis, and antitumor responses, among others. Although it is known that macrophages express CD100 and its receptors, few studies have focused on the role of this semaphorin in this cell type or in macrophage-associated diseases. The aim of this review is to critically revise the available data about CD100 and atherosclerosis, with special emphasis on its roles in macrophages and monocytes. We will also describe the few available data on treatments with anti-CD100 antibodies in different diseases. We hope that this review stimulates future studies on the effects of such an important molecule in a cell type with decisive roles in inflammatory diseases such as atherosclerosis.

Sema4D Knockout Attenuates Choroidal Neovascularization by Inhibiting M2 Macrophage Polarization Via Regulation of the RhoA/ROCK Pathway

“…It is well established that Sema4D and its receptors are expressed in various cell types, including macrophages, and Sema4D has been suggested to be associated with macrophage polarization. 42 A recent study found that Sema4D not only promoted endothelial cell adhesion and migration but also enhanced lactic acid release and induced M2 polarization of macrophages. 43 Another study demonstrated correlations between Sema4D expression and M2 macrophage counts in primary tumors, as well as M2 macrophage percentages in ascites.…”

CD100 modulates cytotoxicity of CD8+ T cells in patients with acute myocardial infarction

“…However, few reports focused on sCD100/mCD100 regulation to T cell function in AMI patients. The extracellular domain of CD100 retained biological activity after shedding from immune cell surface upon activation, resulting in the alteration of macrophage differentiation and phenotype in atherosclerosis [ 13 ] and facilitation of CD8 + T cells activity in chronic hepatitis [ 14 , 33 ]. Thus, sCD100 that is shed from CD8 + T cells in turn promoted CD8 + T cell cytotoxicity, further demonstrating the consequences of CD8 + T cells activation in AMI patients.…”

“…CD100 could be produced by majority of hematopoietic cells, and functions as a ligand by binding to receptors depending on the cell types, including CD72 on lymphoid tissues and plexin B1/B2 on non-lymphoid tissues [ 11 ]. Plaque marcophages and foam cells in human atheomas also express CD100 [ 12 ], which contributes to marcophages-mediated inflammation in atheroscleriosis [ 13 ]. Two forms of CD100 could be found as a membrane-bound dimer (mCD100) or as a soluble molecule (sCD100) originated via proteolytic cleavage by certain factors, especially matrix metalloproteinases (MMPs) [ 14 , 15 ].…”

In vitro: The Modulating Effect of Myricetin on the Atherosclerosis Related Processes in THP1 Macrophages

“…It is defined as a chronic inflammatory condition marked by the development of arterial sclerosis and the release of inflammatory substances secreted by macrophages. Macrophages via its secretions orchestrate the immune response in atherosclerosis [4].…”