The reaction of 16 alpha-hydroxyestrone with erythrocytes in vitro and in vivo.

16 alpha-Hydroxyestrone (16 alpha OHE ) has been shown previously to react with albumin, forming stable covalent adducts with lysine residues. The incubation of [3H]16 alpha OHE with whole blood also results in the incorporation of tritium into cells, with the rate of incorporation paralleling that of 16 alpha OHE -protein adduct formation. 32% of erythrocyte acid-precipitable radioactivity was found to be present within membrane proteins and electrophoresis demonstrated that several of these proteins are modified by [3H]16 alpha OHE . Membrane proteins from the red cells of ten individuals were reduced with sodium borohydride, acid hydrolyzed, and the 16 alpha OHE -lysine adducts purified by hydrophobic chromatography and reverse-phase high-pressure liquid chromatography. The amount of these adducts was quantitated by radioimmunoassay and found to be five times higher than the plasma levels of free 16 alpha OHE . This reflects most likely the accumulation of 16 alpha OHE -protein adducts during the course of the red cell life. Quantitation of 16 alpha OHE -protein adducts with other cellular proteins may contribute to our understanding of systemic lupus erythematosus, an autoimmune disease in which elevated levels of 16 alpha OHE occur.