Cathelicidins are a family of
peptides thought to provide an innate defensive barrier against a variety of potential microbial pathogens. The human and mouse
cathelicidins (LL-37 and
CRAMP, respectively) are expressed at select epithelial interfaces where they have been proposed to kill a number of gram-negative and gram-positive bacteria. To determine if these
peptides play a part in the protection of skin against
wound infections, the anti-microbial activity of LL-37 and
CRAMP was determined against the common
wound pathogen group A Streptococcus, and their expression was examined after cutaneous injury. We observed a large increase in the expression of
cathelicidins in human and murine skin after sterile incision, or in mouse following
infection by group A Streptococcus. The appearance of
cathelicidins in skin was due to both synthesis within epidermal keratinocytes and deposition from granulocyctes that migrate to the site of injury. Synthesis and deposition 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 both 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 are well suited to provide defense against
infections due to group A Streptococcus, and represent an important
element of cutaneous innate immunity.