In mammals, several gene families encode peptides with antibacterial activity, such as the beta-defensins and cathelicidins. These peptides are expressed on epithelial surfaces and in neutrophils, and have been proposed to provide a first line of defence against infection by acting as 'natural antibiotics'. The protective effect of antimicrobial peptides is brought into question by observations that several of these peptides are easily inactivated and have diverse cellular effects that are distinct from antimicrobial activity demonstrated in vitro. To investigate the function of a specific antimicrobial peptide in a mouse model of cutaneous infection, we applied a combined mammalian and bacterial genetic approach to the cathelicidin antimicrobial gene family. The mature human (LL-37) and mouse (CRAMP) peptides are encoded by similar genes (CAMP and Cnlp, respectively), and have similar alpha-helical structures, spectra of antimicrobial activity and tissue distribution. Here we show that cathelicidins are an important native component of innate host defence in mice and provide protection against necrotic skin infection caused by Group A Streptococcus (GAS).

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.

Injectable dermal filler materials consist of either fluids, biological fragments, or suspensions of particles or microspheres. Particles and microspheres are said to "migrate," but migration can occur only when they are injected into blood vessels. To evaluate biocompatibility and transport, five nonresorbable polymethylmethacrylate microspheres of various sizes, suspended in different carriers, as well as resorbable polylactic acid and dextran microspheres were injected subcutaneously into mice. The five implantation sites were the right cheek, right axilla, right groin, urethra, and the right quadriceps muscle of the thigh. These sites were excised along with the local lymph nodes, lungs, liver, and spleen at 1, 3, 6, and 9 months after injection. Polymethylmethacrylate microspheres of 4 microm and 8 microm were phagocytosed but not transported to lymph nodes or distant organs. Larger microspheres of 20, 40, and 100 microm were encapsulated by connective tissue, macrophages, and giant cells. Polylactic acid microspheres caused a mild inflammatory response and had disappeared at 6 months. Dextran microspheres caused a pronounced foreign-body reaction and were phagocytosed at 9 months. The extremely large carbon-coated spheres of 200 to 500 microm in diameter "migrated" up to 1 cm from the implantation site. With the exception of an erroneous intravenous injection, no migration or transportation of any of the injected microspheres to lymph nodes or filter organs was seen. Obviously, the collagen glue released no microspheres. After subdermal injection, the collagen carrier substance kept the microspheres apart as a scaffold for tissue ingrowth, whereas all other carrier substances, such as gelatin, hyaluronic acid, or alginate, separated soon after injection, thereby causing agglomeration of the microspheres.

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