Cathelicidin Antimicrobial Peptides Modulate Angiogenesis

Antimicrobial peptides (AMPs) are effector molecules of the innate immune system. In addition their direct antimicrobial activity AMPs modulate angiogenesis. This chapter reviews the current knowledge about the link between AMPs and angiogenesis. A variety of AMPs have been isolated from species of all kingdoms and are classified based on their structure and amino acid motifs. AMPs have a broad antimicrobial spectrum and lyse microbial cells by interaction with biomembranes. Cathelicidins are characterized by a conserved N-terminal cathelin domain and a variable C-terminal antimicrobial domain that can be released from the precursor protein after cleavage by proteinases. LL-37 is the C-terminal part of the only human cathelicidin identified to date called human cationic antimicrobial protein (hCAP-18) and was first isolated from polymorphonuclear leukocytes but is also expressed by lymphocytes, macrophages and epithelial cells. LL-37 inactivates microorganisms by interaction with biomembranes. Beside the antimicrobial activity LL-37 modulates inflammation and displays different important cellular activities such as acting as chemotractant or activator of epithelial or immune cells. LL-37 interacts with endothelial cells and stimulates angiogenesis both in vitro and in vivo. LL-37 stimulates collateral formation in a rabbit hind-limb model of ischemia. Mice deficient for the murine analogue of LL-37/hCAP-18 showed decreased neovascularization of skin lesions as compared to wild-type controls. The angiogenic actions of LL-37 seem to be receptor-mediated by interaction with formyl peptide receptor–like 1 (FPRL1) that is expressed on endothelial cells. Cathelicidin is an example that AMPs serve as multifunctional host defense molecules and link antibiotic activity, repair and angiogenesis