THE HUMAN GENE FALL39 AND PROCESSING OF THE CATHELIN PRECURSOR TO THEANTIBACTERIAL PEPTIDE LL-37 IN GRANULOCYTES

The peptide FA-LL-37, previously termed FALL-39, was originally predic ted from an ORF of a cDNA clone isolated from a human bone marrow libr ary. This peptide was synthesized and found to have antibacterial acti vity. We have now characterized and sequenced the complete gene for FA -LL-37, termed FALL39. It is a compact gene of 1963 bp with four exons . Exons 1-3 code for a signal sequence and the cathelin region. Exon 4 contains the information for the mature antibacterial peptide. Our re sults indicate that FALL39 is the only member of the cathelin gene fam ily present in the human genome. Potential binding sites for acute-pha se-response factors are identified in the promoter and in intron 2. A possible role for the cytokine interleukin-6 in the regulation of FALL 39 is discussed. Anti-(FA-LL-S7) Ige located the peptide in granulocyt es and we isolated the mature peptide from these cells after degranula tion. Structural analysis determined the mature peptide to be LL-37. T o obtain LL-37 for antibacterial assays, synthetic FA-LL-37 was degrad ed with dipeptidyl-peptidase I. This analysis showed that mature LL-37 is a potent antibacterial peptide.