High Expression Of Macrophage Function-Related Protein MS4A4A By Monocytes In Rheumatoid Arthritis Disease Process

ObjectiveTo investigate the changes of in peripheral blood mononuclear cells and their three subsets during the disease process of rheumatoid arthritis;To detect the expression of MS4A4A molecules on peripheral blood mononuclear cells of rheumatoid arthritis patients by flow cytometry;To verify whether MS4A4A molecules are up-regulated during the polarization of mononuclear cells to M2 type macrophages by in vitro experiments.MethodsForty-two patients with rheumatoid arthritis and thirty healthy controls were selected for this study.Human venous blood was collected from patients with rheumatoid arthritis and healthy controls,and the percentage of monocytes,T cells,NKT cells and NK cells in peripheral blood mononuclear cells(PBMCs)was measured by flow cytometry in healthy controls and patients with rheumatoid arthritis,and the differences between them were compared.The ratios of peripheral blood monocytes and their three subsets:CD14bright CD16-monocytes,CD14bright CD16+ monocytes and CD14dim CD16+ monocytes were examined in healthy controls and rheumatoid arthritis patients;the expression of MS4A4A on peripheral blood lymphocytes and monocytes was analysed in healthy controls and rheumatoid arthritis patients,respectively.In vitro,THP-1 cells at logarithmic growth stage were induced with LPS and PMA for 24h,followed by IFN-γ and IL-4 for 48h to differentiate into M1 and M2 macrophages.M2-type macrophages,and the expression of MS4A4A molecules was analyzed by flow cytometry assay.Data are presented as mean± standard deviation,and an unpaired t-test was used between two subgroups.Results1.The proportion of monocytes in peripheral blood was significantly ri sen in RA patients compared to healthy controls[(14.7%±1.37%)vs(5.91%±1.52%),(P<0.01)].2.The proportion of CD14brightCD16-monocytes in peripheral blood mononuclear cells was significantly reduced in RA patients compared to healthy controls[(73.99%±12.34%)vs(88.2%±6.94),(P<0.01)];the proportion of CD14bright CD16+monocytes was significantly increased compared to healthy controls[(11.5%±9.91%)vs(4.91%±3.2%),(P<0.05)];CD14dimCD16+monocyte proportion was significantly increased compared to healthy controls[(14.53%±6.78%)vs(6.7%±4.16%),(P<0.001)].3.The enhanced expression of MS4A4A molecules on the surface of peripheral blood mononuclear cells in RA patients compared to healthy controls[(7.08%±5.06%)vs(1.15%±0.94%),(P<0.001)].4.The enhanced expression of MS4A4A molecules by CD14bright CD16monocytes[(8.64%±6.71%)vs(3.32%±1.99%),(P<0.05)],CD14dim CD16+monocytes[(30.11%±17.15%)vs(8.01%±3.88%),(P<0.001)]in the peripheral blood of RA patients compared to healthy controls.5.The process of polarization of monocytes to macrophages could lead to enhanced of the expression of MS4A4A molecules,especially in M2 type macrophages with increased expression(P<0.01).ConclusionsMS4A4A molecules are up-regulated in the expression of CD14bright CD16 monocytes as well as CD14dim CD16+ monocytes subsets in peripheral blood of rheumatoid arthritis patients.By in vitro experiments,MS4A4A molecules were enhanced in monocytes during their polarization to M2-type macrophages.