Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A Streptococcus

Cathelicidins are a family of peptides thought to provide an innate defensi ve barrier against a variety of potential microbial pathogens. The human an d mouse cathelicidins (LL-37 and CRAMP, respectively) are expressed at sele ct epithelial interfaces where they have been proposed to kill a number of gram-negative and gram-positive bacteria. To determine if these peptides pl ay a part in the protection of skin against wound infections, the anti-micr obial activity of LL-37 and CRAMP was determined against the common wound p athogen group A Streptococcus, and their expression was examined after cuta neous injury. We observed a large increase in the expression of cathelicidi ns in human and murine skin after sterile incision, or in mouse following i nfection by group A Streptococcus. The appearance of cathelicidins in skin was due to both synthesis within epidermal keratinocytes and deposition fro m granulocyctes that migrate to the site of injury. Synthesis and I deposit ion in the wound was accompanied by processing from the inactive prostorage form to the mature C-terminal peptide, Analysis of anti-microbial activity of this C-terminal peptide against group A Streptococcus revealed that bot h LL-37 and CRAMP potently inhibited bacterial growth. Action against group A Streptococcus occurred in conditions that typically abolish the activity of anti-microbial peptides against other organisms. Thus, cathelicidins ar e well suited to provide defense against infections due to group A Streptoc occus, and represent an important element of cutaneous innate immunity.