Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide.
Cathelicidins (caths) are peptides that are expressed at high levels in neutrophils and some epithelia and can act as natural antibiotics by directly killing a wide range of microorganisms. We hypothesized that caths are expressed in mast cells (MCs), because these cells have been previously associated with inherent antimicrobial activity. Cultured murine MCs contained abundant amounts of cathelin-related antimicrobial peptide (AMP), the murine cath, and this expression was inducible by LPS or lipoteichoic acid. Human skin MCs also expressed cath as detected by immunohistochemical analysis for the human cath LL-37. The functional significance of this expression was shown by comparing MCs cultured from normal mice to MCs from littermates deficient in the cathelin-related AMP gene (Cnlp(-)). MCs derived from Cnlp(-/-) animals had a 50% reduction in their ability to kill group A STREPTOCOCCUS: These MCs expressed equivalent amounts of mRNA for murine beta-defensin-4, a beta-defensin AMP. Thus, different antimicrobials can be identified in MCs, and the presence of cath is necessary for efficient bacterial killing. These observations suggest that the presence of cath is vital to the ability of mammalian MCs to participate in antimicrobial defense.
Di Nardo
Anna
A
Division of Dermatology, Department of Medicine, University of California and Veterans Affairs Medical Center, San Diego, CA 92161, USA.
Vitiello
Antonella
A
Gallo
Richard L
RL
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis / Q000502:physiology; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D054804:Cathelicidins; D002478:Cells, Cultured; D006801:Humans; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008826:Microbial Sensitivity Tests; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D013297:Streptococcus pyogenes / Q000187:drug effects / Q000254:growth & development; D023083:beta-Defensins / Q000096:biosynthesis / Q000502:physiology
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; C106641:DEFB4A protein, human; D011506:Proteins; D023083:beta-Defensins