Human cathelicidin antimicrobial peptide (hCAP18, also known as CAMP) is synthesized as 18-kDa pro-protein (Sorensen O et al. 1997, 2001; Yang D et al. 2000; Mendez-Samperio P 2010). The proform hCAP18 is stored within vesicles such as specific granules of neutrophils. Upon inflammation or injury hCAP18 undergoes proteolytic cleavage to produce the mature antimicrobial 37-amino acid-long peptide LL-37 (CAMP(134-170)) which is secreted outside the cells (Sorensen O et al. 1997, 2001; Yang D et al. 2000; Mendez-Samperio P 2010). LL-37 has a net positive charge and is thought to interact with bacteria via electrostatic attraction toward the negatively charged bacterial membrane (Wang G et al. 2012, 2014; Kuroda K et al. 2015). LL-37 is amphiphilic in nature and is comprised of hydrophobic and hydrophilic residues aligned on opposite sides of the peptide (Braff MH et al. 2005; Wang G 2008; Wang G et al. 2012, 2014). The hydrophobic domain may facilitate the peptide penetration through phospholipid bilayers of bacteria (Shai Y 1999).
LL-37 has direct microbicidal activities against Gram-positive bacteria (S. aureus, Group A Streptococcus, Bacillus megaterium), Gram-negative bacteria (E. coli, P. aeruginosa, Salmonella minnesota) and fungi such as C. albicans (Yang D et al. 2000; Nagaoka I et al. 2005; Braff MH et al. 2005; Wang G et al. 2012). LL-37 also has antiviral activities against herpes simplex virus, HIV-1, and vaccinia virus (Yasin B et al. 2000; Steinstraesser L et al. 2005; Howell MD et al. 2006; Gordon YJ et al. 2005). LL-37 may have the potential to prevent sepsis or septic shock associated with pathogenic bacterial infection by inhibiting the release of toxic components such as LPS and lipoteichoic acid (LTA) that cause excess tissue damage and inflammation (Larrick JW et al. 1995)
LL-37 expression was found to correlate with an activation of TLR2, TLR4 and TLR9 signaling pathways in M. tuberculosis-stimulatied human monocyte-derived macrophages, alveolar macrophages and neutrophils (Rivas-Santiago et al. 2008).
