Apolipoprotein A-I binds and inhibits the human antibacterial/cytotoxic 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 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.
Wang
Y
Y
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Agerberth
B
B
Löthgren
A
A
Almstedt
A
A
Johansson
J
J
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000378:metabolism*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D054804:Cathelicidins; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D000970:Antineoplastic Agents; D016632:Apolipoprotein A-I; D002352:Carrier Proteins; D054804:Cathelicidins