Cathelicidins: a family of endogenous antimicrobial peptides.
The cytoplasmic granules of mammalian neutrophils contain several antimicrobial peptides. Some, like defensins, are fully processed before storage, whereas others are stored as precursors that require additional processing. Cathelicidins are bipartite molecules with an N-terminal cathelin domain and an antimicrobial C-terminal domain. Humans apparently have only one cathelicidin gene. Its product, hCAP-18, is present in the secondary (specific) granules of neutrophils, and its C-terminal antimicrobial peptide, LL-37, is liberated by proteinase 3 coincident with degranulation and secretion. Many nonmyeloid tissues also express hCAP-18, including epididymis, spermatids, keratinocytes, epithelial cells, and various lymphocytes. LL-37 stimulates chemotaxis, acting via the formyl peptide-like receptor-1. The structurally diverse cathelicidin-derived antimicrobial peptides of animals provide interesting models for pharmaceutical development. PR-39, a proline-rich porcine cathelicidin, has shown efficacy in limiting myocardial damage after experimental ischemia in rodent models. Porcine protegrins are in stage III clinical trials to prevent oral mucositis caused by radiation or chemo-therapy.
Lehrer
Robert I
RI
Department of Medicine, Molecular Biology Institute, University of California at Los Angeles, Los Angeles, California, USA. rlehrer@mednet.ucla.edu
Ganz
Tomas
T
D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000502:physiology*; D001798:Blood Proteins / Q000502:physiology; D054804:Cathelicidins; D002634:Chemotaxis, Leukocyte; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009504:Neutrophils / Q000276:immunology; D010455:Peptides; D011506:Proteins / Q000627:therapeutic use
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D054804:Cathelicidins; D010455:Peptides; D011506:Proteins; C403305:SMAP29 protein, Ovis aries; C072212:PR 39; C119872:antimicrobial peptide IB-367