Heparan Sulfate Proteoglycan–Involving Immunomodulation by Cathelicidin Antimicrobial Peptides LL-37 and PR-39

Antimicrobial peptides, which are categorized by homologous structural motifs, are effector molecules of innate immunity with direct antimicrobial activity and multiple other functions. The most prominent families are defensins and cathelicidins. These peptides are expressed in the granules of several types of leukocytes and in a wide variety of tissue types[1]. Peptide antibiotics of the cathelicidin family are characterized by a highly conserved signal sequence and proregions (“cathelin” = cathepsin L inhibitor), but show substantial heterogeneity in the carboxy-terminal domain that encodes the mature peptide[2,3,4]. Based on amino acid sequences, cathelicidin peptides are categorized in (a) linear, a-helical peptides without cysteines, e.g., LL-37/human cathelicidin antimicrobial peptide (hCAP)-18 from human; (b) peptides with an even number of cysteines linked by disulfide bridges, e.g., protegrins (porcine cathelicidin peptides); and (c) peptides with an unusually high proportion of one or two amino acids, e.g., PR-39 from porcine leukocytes (Table 1).