LL-37

LL-37 is the endogenous cathelicidin peptide: the 37-residue C-terminal domain (C205H340N60O53, about 4,493 g/mol) of the 18 kDa cationic antimicrobial protein precursor hCAP-18. Cathelicidins share a highly conserved N-terminal pre-pro region homologous to cathelin and a variable C-terminal domain that carries their antimicrobial and immunomodulatory activity. In neutrophils, hCAP-18 is stored in peroxidase-negative granules and is cleaved after exocytosis by the serine protease proteinase 3 to release LL-37. The precursor is also produced by epithelial cells of the skin, respiratory tract and gastrointestinal tract.

LL-37 in the research literature

Beyond direct activity against bacteria, fungi and viruses, LL-37 has been studied as a signaling molecule in innate immunity. In cell-based assays it induced calcium mobilization and chemotaxis in monocytes, neutrophils and T cells, and in HEK293 cells transfected with formyl peptide receptor-like 1 (FPRL1), identifying FPRL1 as one of its receptors. Reviews describe additional roles in modulating inflammatory responses and leukocyte chemo-attraction, and structure-activity work has examined shorter fragments of the LL-37 domain such as SK-24, IV-20 and FK-13.

Because native LL-37 shows limited proteolytic stability and cytotoxicity in some assays, peptide-design studies have explored truncated and retro-analogs and nanoscale carrier systems.