Multispecific myeloid defensins.
OBJECTIVE
This review describes recent progress in our understanding of defensins and their contributions to innate immunity. Defensins are small, cysteine-rich endogenous antibiotic peptides. Human neutrophils contain large amounts of three alpha-defensins (HNP-1-HNP-3), and smaller amounts of a fourth, HNP-4. Monocytes and macrophages generally lack defensins, but they release messengers that induce the synthesis of beta-defensins in epithelial cells.


RESULTS
In addition to their antimicrobial and immunomodulatory effects, HNP-1-HNP-3 possess antiviral and toxin-neutralizing properties. Induction of beta-defensins in epithelial cells is mediated by cell-surface Toll-like receptors or cytoplasmic peptidoglycan receptors that can recognize pathogen-associated molecules. Mutations in Nod2, a cytoplasmic peptidoglycan receptor, are associated with reduced levels of intestinal alpha-defensins and ileal Crohn's disease. Human defensin genes show marked copy-number polymorphism. High level constitutive expression of defensins may afford protection against HIV-1 and other defensin-sensitive pathogens. Theta-defensins (cyclic octadecapeptides found in nonhuman primates) have impressive antiviral and antitoxic properties.


CONCLUSIONS
The multiple properties of defensins contribute to human innate immunity against bacteria, bacterial toxins, and viruses.
Lehrer
Robert I
RI
David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA. rlehrer@mednet.ucla.edu
D000818:Animals; D001424:Bacterial Infections / Q000276:immunology; D023082:Defensins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D014777:Virus Diseases / Q000276:immunology
D023082:Defensins