INTRACELLULAR DELIVERY OF LIPOPOLYSACCHARIDE DURING DNA TRANSFECTION ACTIVATES A LIPID A-DEPENDENT CELL-DEATH RESPONSE THAT CAN BE PREVENTED BY POLYMYXIN-B

The presence of lipopolysaccharide (LPS) as a contaminant in plasmid D NA prepared from Escherichia coli is well documented, and we have prev iously demonstrated that LPS internalization during adenovirus-mediate d gene transfer can generate a toxicity in some primary cell types. We demonstrate here that in addition to adenoviral systems, several comm only used nonviral methods of gene transfer also activate this cell de ath response in the presence of LPS. Subcomponents of LPS were analyze d and the toxicity was found to be due to the lipid A component of LPS . The LPS-chelating antibiotic polymyxin B, when present at concentrat ion of 10-30 mu g/ml, can block this toxicity.