The study found that a common blood protein, apolipoprotein A‑I (apoA‑I), sticks to the human antimicrobial peptide LL‑37 and cuts its ability to kill bacteria in half when both are at the same level. This binding happens in normal plasma, not because the peptide is broken down, and blocking apoA‑I with antibodies restores LL‑37’s activity. For people experimenting with LL‑37 as a supplement or therapy, the results suggest that the peptide’s effectiveness could be limited when it circulates in the blood.

The antibacterial and cytotoxic activity of the human cathelicidin peptide LL-37 is inhibited by plasma. Because LL-37 does not undergo rapid degradation in human plasma, we postulated that this inhibition results from binding of LL-37 to unidentified proteins. An LL-37 binding plasma protein has now been isolated by affinity chromatography. SDS-polyacrylamide gel electrophoresis 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 analysis using surface plasmon resonance showed that LL-37 and isolated apoA-I bind with an apparent Kd in the low micromolar range. 50 microM of apoA-I inhibits the antibacterial activity of 50 microM LL-37 by about 50% of the inhibition exhibited by plasma. In addition, anti-apoA-I IgG completely blocks the plasma inhibition of LL-37 antibacterial activity up to a peptide concentration of 25 microM and blocks most of the plasma inhibition at higher LL-37 concentrations. These results indicate that apoA-I is the main LL-37 binding protein in human plasma and may work as a scavenger of LL-37, thus suggesting a novel mechanism involved in the regulation of a cathelicidin peptide.