posted 07-15-2011 08:12 PM            

Antimicrobial peptides are ancient and potent weapons of the innate immunity of all life forms (1–4). In mammals, defensins and cathelicidins are the two major families of antimicrobial peptides. While several cathelicidins were found in animals such as sheep, cow, and pig, only one cathelicidin was identified in humans (5). The precursor proteins of the cathelicidin family share a highly conserved N-terminal “cathelin” domain, but have a highly variable C-terminal antimicrobial region. Upon bacterial insult, human cathelicidin LL-37 (named based on the first two amino acids in the sequence followed by the number of residues in the peptide) is released by proteases from its precursor hCAP-18 (i.e. human cationic antimicrobial protein, ~18 kDa). The importance of this host defense peptide to human health is now firmly established. Patients lacking this molecule are more susceptible to infections (6). While cathelicidin knock-out mice are more readily infected (7), expression of additional cathelicidins protects the animals from infection (8). LL-37 also associates with lipopolysaccharides (or endotoxin) and protects rats from sepsis caused by bacteria (9). LL-37 is also reduced in cystic fibrosis airways as a result of direct interaction with DNA and filamentous F-actin (10).

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Reference
1. Boman, H. G. (1995) Annu. Rev. Immunol.13, 61-92
2. Sambhara, S., and Lehrer, R. I. (2007) Expert Rev Anti Infect Ther.5, 1-5
3. Hancock, R. E. W. (2001) Lancet. Infect. Dis. 1, 156-164
4. Zasloff, M. (2002) Nature 415, 389-395
5. Zanetti, M. (2005) Curr. Issues Mol. Biol. 7, 179-196
6. Pütsep, K., et al. (2002) Lancet 360, 1144-1149
7. Nizet, V., et al. (2001) Nature414, 454-457
8. Lee, P.H., et al. (2005) Proc. Natl. Acad. Sci. U. S. A.102, 3750-3755
9. Cirioni, O., et al. (2006) Antimicrob. Agents Chemother. 50, 1672-1679
10. Bucki, R., et al. (2007) Eur. Respir. J.29, 624-632

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