Apolipoprotein A-I binds and inhibits the human antibacterial/cytotolic peptide LL-37

The antibacterial and cytotoxic activity of the human cathelicidin peptide LL-37 is inhibited by plasma. Because LL-37 does not undergo rapid degradat ion in human plasma, we postulated that this inhibition results from bindin g of LL-37 to unidentified proteins. An LL-37 binding plasma protein has no w been isolated by affinity chromatography, SDS-polyacrylamide gel electrop horesis of proteins that bound to an LL-37 column revealed one band with a molecular mass of about 26 kDa, and amino acid sequence analysis identified the protein as apolipoprotein A-I (apoA-I), Biomolecular interaction analy sis using surface plasmon resonance showed that LL-37 and isolated apoA-I b ind with an apparent K-d in the low micromolar range. 50 mu M of apoA-I inh ibits the antibacterial activity of 50 mu M LL-37 by about 50% of the inhib ition exhibited by plasma. In addition, anti-apoA-I IgG completely blocks t he plasma inhibition of LL-37 antibacterial activity up to a peptide concen tration of 25 mu m and blocks most of the plasma inhibition at higher LL-37 concentrations. These results indicate that apoA-I is the main LL-37 bindi ng protein in human plasma and may work as a scavenger of LL-37, thus sugge sting a novel mechanism involved in the regulation of a cathelicidin peptid e.