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, gastrointestinal tract and bronchial tree produces a number of antibacterial peptides, and our phagocytic neutrophils rapidly ingest and enzymatically degrade invading organisms, as well as produce peptides and enzymes with antimicrobial activities. Some of these antimicrobial moieties also appear to alert host cells involved in both innate host defense and adaptive immune responses. The epithelial cells are a source of constitutively produced beta defensin (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 enzymes cathepsin G and chymase, azurocidin, a defensins and cathelicidin. In contrast, C5a and C3b are produced by activation of the serum complement cascade. The antimicrobial moieties direct the migration and activate target cells by interacting with selected G-protein-coupled seven-transmembrane receptors (GPCRs) on cell surfaces. The beta defensins interact with the CCR6 chemokine GPCRs, whereas cathelicidins interact with the low-affinity FPRL-1 receptors. The neutrophil-derived cathepsin G acts on the high-affinity FMLP receptor (GPCR) known as FPR, while the receptors for chymase and 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 mediating chemotaxis also activate receptor-expressing cells to produce other mediators of inflammation.
Yang
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Laboratory of Molecular Immunoregulation, National Cancer Institute at Frederick, Maryland 21702-1201, USA.
Chertov
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Oppenheim
J J
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D000818:Animals; D000890:Anti-Infective Agents / Q000276:immunology*; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins / Q000276:immunology / Q000502:physiology; D002352:Carrier Proteins / Q000276:immunology / Q000502:physiology; D056649:Cathepsin G; D002403:Cathepsins / Q000276:immunology / Q000502:physiology; D053818:Chymases; D003165:Complement System Proteins / Q000276:immunology / Q000502:physiology; D023082:Defensins / Q000276:immunology / Q000502:physiology; D006801:Humans; D007110:Immunity, Active; D007113:Immunity, Innate; D008322:Mammals; D010455:Peptides / Q000276:immunology / Q000502:physiology*; D011506:Proteins / Q000276:immunology / Q000502:physiology*; D012697:Serine Endopeptidases / Q000276:immunology / Q000502:physiology
C062991:AZU1 protein, human; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D023082:Defensins; D010455:Peptides; D011506:Proteins; D003165:Complement System Proteins; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D053818:Chymases