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.
*Department of Medicine, † Molecular Biology Institute, and ‡ Department of Pathology, University of California at Los Angeles, Los Angeles, California, USA.
Correspondence to Robert I. Lehrer, MD, Department of Medicine, Room CHS 37-062, UCLA Center for the Health Sciences, Los Angeles, CA 90095, USA; e-mail: firstname.lastname@example.org
Robert I. Lehrer and Tomas Ganz consult for and hold stock in IntraBiotics Pharmaceuticals, Mountain View, CA, a company developing protegrin-based therapeutics under license from the University of California.