The role of mammalian antimicrobial peptides and proteins in awakening of innate host defenses and adaptive immunity

Since we live in a dirty environment, we have developed many host defenses to contend with microorganisms. The epithelial lining of our skin, gastroin testinal tract and bronchial tree produces a number of antibacterial peptid es, and our phagocytic neutrophils rapidly ingest and enzymatically degrade invading organisms, as well as produce peptides and enzymes with antimicro bial activities. Some of these antimicrobial moieties also appear to alert host cells involved in both innate host defense and adaptive immune respons es. The epithelial cells are a source of constitutively produced beta defen sin (HBD1) and proinflammatory cytokine-inducible beta defensins (HBD2 and -3) and cathelicidin (LL37). The neutrophils-derived antimicrobial peptides are released on demand from their cytoplasmic granules. They include the e nzymes cathepsin G and chymase, azurocidin, alpha defensins and cathelicidi n. In contrast, C5a and C3b are produced by activation of the serum complem ent cascade. The antimicrobial moieties direct the migration and activate t arget cells by interacting with selected G-protein-coupled seven-transmembr ane receptors (GPCRs) on cell surfaces. The beta defensins interact with th e CCR6 chemokine GPCRs, whereas cathelicidins interact with the low-affinit y FPRL-1 receptors. The neutrophil-derived cathepsin G acts on the high-aff inity FMLP receptor (GPCR) known as FPR, while the receptors for chymase an d azurocidin have not been identified as yet. The serum-derived C5a uses a GPCR known as C5aR to mediate its chemotactic and cell-activating effects. Consequently, all these ligand-receptor interactions in addition to mediati ng chemotaxis also activate receptor-expressing cells to produce other medi ators of inflammation.