Influence And Mechanism Of Different Macrophage Phenotype On Foam Cell Formation In Atherosclerosis

Objective:The present study was to investigate the influence and mechanism of different macrophage phenotype on foam cells formation in atherosclerosis.Methods:Monocytes induced into macrophages by M-CSF.Macrophages were cultured with IFN-γ plus LPS for classically activated macrophages(M1) or with IL-4 for alternatively activated macrophages(M2).M1 and M2 macrophages were cultured in DMEM medium containing 10% fetal bovine serum,and then treated with ox-LDL for 48 h,respectively.The cellular lipid accumulation was showed by oil red O staining and the cellular contents of TC、FC and CE were examined by HPLC.The m RNA and protein expression of CD36 and SR-A1 were detected by real-time PCR and Western blot,respectively.The expression of GRP94 and GRP78 which were molecular markers of ERS, was detected by Western blotResults:M2 macrophages have a higher capacity to accumulate lipids. After exposure to oxidized LDL for 48 h,M2 macrophages showed intense Oil-Red-O staining indicating extensive intracellular lipid accumulation.When compared with M1 macrophages, the content of intracellure TC 、 FC and CE increased dramatically in M2 macrophages through measurement of HPLC(P<0.05). The m RNA and protein expression of CD36 and SR-A1 was higher in M2 macrophages as compared to M1 macrophages.As compared to M1 macrophages,gene expression levels of the GRP94 and GRP78 were higher in M2 macrophages.Conclusion:When exposured to oxidized LDL,M2 macrophages are more susceptible to foam cell formation than M1 macrophages. The mechanism may be that CD36 and SR-A1 upregulation in M2 macrophage induced by ERS enhances the foam cell formation by uptaking more ox-LDL.