NEUTRALIZATION AND TRANSFER OF LIPOPOLYSACCHARIDE BY PHOSPHOLIPID TRANSFER PROTEIN

Phospholipid transfer protein (PLTP) and lipopolysaccharide-binding pr otein (LBP) are lipid transfer proteins found in human plasma. PLTP sh ares 24% sequence similarity with LBP. PLTP mediates the transfer and exchange of phospholipids between lipoprotein particles, whereas LBP t ransfers bacterial lipopolysaccharide (LPS) either to lipoprotein part icles or to CD14, a soluble and cell-surface receptor for LPS, We aske d whether PLTP could interact with LPS and mediate the transfer of LPS to lipoproteins or to CD14, PLTP was able to bind and neutralize LPS: incubation of LPS with purified recombinant PLTP (rPLTP) resulted in the inhibition of the ability of LPS to stimulate adhesive responses o f neutrophils, and addition of rPLTP to blood inhibited cytokine produ ction in response to LPS. Transfer of LPS by rPLTP was examined using fluorescence dequenching experiments and native gel electrophoresis. T he results suggested that rPLTP was able to mediate the exchange of LP S between micelles and the transfer of LPS to reconstituted HDL partic les, but it did not transfer LPS to CD14. Consonant with these finding s, rPLTP did not mediate CD14-dependent adhesive responses of neutroph ils to LPS. These results suggest that while PLTP and LBP both bind an d transfer LPS, PLTP is unable to transfer LPS to CD14 and thus does n ot mediate responses of cells to LPS.