Cutting Edge: Mast Cell Antimicrobial Activity Is Mediated by Expression of Cathelicidin Antimicrobial Peptide 1

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 β-defensin-4, a β-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.

[1]  C. Garbe,et al.  Cathelicidin anti-microbial peptide expression in sweat, an innate defense system for the skin. , 2002, The Journal of investigative dermatology.

[2]  Tomas Ganz,et al.  Endogenous antimicrobial peptides and skin infections in atopic dermatitis. , 2002, The New England journal of medicine.

[3]  R. Hancock,et al.  The Human Antimicrobial Peptide LL-37 Is a Multifunctional Modulator of Innate Immune Responses1 , 2002, The Journal of Immunology.

[4]  R. Gallo,et al.  Cathelicidins, essential gene-encoded mammalian antibiotics , 2002, Journal of Molecular Medicine.

[5]  K. Iwabuchi,et al.  A cathelicidin family of human antibacterial peptide LL‐37 induces mast cell chemotaxis , 2002, Immunology.

[6]  M. Arock,et al.  The role of mast cells in host defense and their subversion by bacterial pathogens. , 2002, Trends in immunology.

[7]  J. Marshall,et al.  Toll‐like receptor 4‐mediated activation of murine mast cells , 2001, Journal of leukocyte biology.

[8]  Takaaki Ohtake,et al.  Innate antimicrobial peptide protects the skin from invasive bacterial infection , 2001, Nature.

[9]  E. Noga,et al.  Antimicrobials: Peptide antibiotics in mast cells of fish , 2001, Nature.

[10]  F. Uckun,et al.  Role of Janus kinase 3 in mast cell-mediated innate immunity against gram-negative bacteria. , 2001, Immunity.

[11]  V. Nizet,et al.  Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A Streptococcus. , 2001, The Journal of investigative dermatology.

[12]  J. McLachlan,et al.  Studies of the multifaceted mast cell response to bacteria. , 2001, Current opinion in microbiology.

[13]  Ji Ming Wang,et al.  Ll-37, the Neutrophil Granule–And Epithelial Cell–Derived Cathelicidin, Utilizes Formyl Peptide Receptor–Like 1 (Fprl1) as a Receptor to Chemoattract Human Peripheral Blood Neutrophils, Monocytes, and T Cells , 2000, The Journal of experimental medicine.

[14]  S. Abraham,et al.  Role of mast cell leukotrienes in neutrophil recruitment and bacterial clearance in infectious peritonitis , 2000, Journal of leukocyte biology.

[15]  P. A. van der Merwe,et al.  The mast cell tumor necrosis factor alpha response to FimH-expressing Escherichia coli is mediated by the glycosylphosphatidylinositol-anchored molecule CD48. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[16]  R. Bals,et al.  Transfer of a cathelicidin peptide antibiotic gene restores bacterial killing in a cystic fibrosis xenograft model. , 1999, The Journal of clinical investigation.

[17]  S. Abraham,et al.  Clinical implications of mast cell–bacteria interaction , 1998, Journal of Molecular Medicine.

[18]  C. Kozak,et al.  Identification of CRAMP, a Cathelin-related Antimicrobial Peptide Expressed in the Embryonic and Adult Mouse* , 1997, The Journal of Biological Chemistry.

[19]  S. Galli,et al.  Identification of a Committed Precursor for the Mast Cell Lineage , 1996, Science.

[20]  J. Odeberg,et al.  FALL-39, a putative human peptide antibiotic, is cysteine-free and expressed in bone marrow and testis. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[21]  R. Lehrer,et al.  Mouse neutrophils lack defensins , 1992, Infection and immunity.

[22]  H. Horstmann,et al.  Bactenecins, defense polypeptides of bovine neutrophils, are generated from precursor molecules stored in the large granules , 1990, The Journal of cell biology.