Monocytes and macrophages are implicated in cardiovascular disease, including atherosclerotic plaque progression and regression. The scavenger receptor CD36, which is highly expressed in macrophages, mediates lipid uptake into macrophages and promotes clearance of apoptotic and dead cells. Moreover, CD36 as multi-ligand scavenger receptor binds both fatty acids and lipoproteins, which differ in their effects on macrophage phenotype. Some in vitro experiments have reported that CD36-mediated uptake of lipids convert macrophages to an inflammatory phenotype, whereas other studies show that lipid uptake converts macrophages to an alternatively activated state. To determine the role of this receptor in vivo where cells are exposed to both lipoproteins and free fatty acids, we created macrophage-specific CD36 knockout mice. Using zymosan-induced peritonitis to challenge immune cells, we found a broad heterogeneity of resident and infiltrated immune cells, primarily macrophages, in the peritoneum 72h after the initial stimuli. Macrophage
CD36
deficient cells had increased expression of pathways related to innate immunity, antigen presentation and oxidative phosphorylation; whereas pathways related to efferocytosis adaptive immunity and B cell activation were downregulated. Gene signatures related to pro-inflammatory features were evident only in CD36 deficient macrophages. Macrophage efferocytosis capacity and B cell antibody production did not differ between control and CD36 depleted mice. Our data show that CD36 expression allows macrophages to convert to a less inflammatory state.
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