キレート剤と界面活性剤によるエンドトキシンの活性低下 (Low Endotoxin Recoveryの機序)

抄録

 Low Endotoxin Recovery (LER) is a phenomenon of endotoxin activity decrease in a matrix containing a chelating agent and a detergent, and is a controversial topic in the biopharmaceutical field. The mechanism of LER is not fully elucidated. When endotoxin in LER solutions was diluted with water, the activity was decreased. The activity was maintained for a long time at 4°C, and was recovered by magnesium dilution and direct addition to the Limulus amebocyte lysate (LAL). The size of endotoxin in LER solution was not changed after the activity was decreased. Considering these results, a new LER mechanism was proposed. A chelating agent removes divalent cations from the surface of endotoxin aggregates, and endotoxin molecules on the surface of the aggregates are replaced with detergent molecules. The reduction of the surface area of endotoxin aggregates causes decrease of the endotoxin activity to the LAL.