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Objectives To study the interaction of beta-2-glycoprotein Ⅰ (β2GP Ⅰ) with the membrane of hepatocytes and determine whether β2GP Ⅰ participates in HBV infection.Methods Ligand blotting, fluorescence microscopy, and fluorescence activated cell sorter (FACS) analysis were used to detect the specific interaction of β2GP Ⅰ with the hepatoma cell line smmc7721, the gastric carcinoma cell line SGC7901, and the lymphoma cell line HL-60.Results A specific 40 kDa β2GP Ⅰ band was observed by ligand blotting in the case of smmc7721 cells. No such band was observed in SGC7901 or HL-60 cells. Fluorescence microscopy also revealed specific binding of FITC-β2GP Ⅰ to smmc7721 cells, but neither to SGC7901 nor HL-60 cells. FACS analysis demonstrated that the binding rate of FITC-β2GP Ⅰ to smmc7721 cells was significantly higher than these in SGC7901 and HL-60 cells (P<0.01). The binding rate to smmc7721 cells did not increase with increasing amounts of FITC-β2GP Ⅰ.Conclusions There is a specific β2GP Ⅰ-binding protein on the membrane of hepatoma cells in cell line smmc7721 which as the β2GP Ⅰ receptor may participate in HBV infection of hepatocytes.