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

Abstract

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.

Cathelicidin Antimicrobial Peptides Block Dendritic Cell TLR4 Activation and Allergic Contact Sensitization

“…The ability of cathelicidin to function as an antimicrobial peptide is required for optimal host defense against infection both in vitro and in vivo (1,24,25). However, recent in vitro studies indicate that cathelicidin can also modulate host inflammatory responses.…”

“…A lack of cathelicidin antimicrobial peptides has been associated with an increase in microbial growth in both mouse models of invasive bacterial infection and in isolated cell culture systems (1,24,25). In addition, a lack of cathelicidin and other antimicrobial peptides correlates with increased infections in patients with atopic dermatitis or Kostman syndrome (19,35).…”

Mast cells initiate early anti-Listeria host defences

“…The capacity of mast cells to directly kill bacteria via phagocytosis (Feger et al, 2002) or secretion of antimicrobial peptides has been reported (Di Nardo et al, 2003). To better understand the underlying mechanisms in listerial control, the role of mast cell-mediated phagocytosis in the clearance of L. m. was evaluated.…”

Angiogenesis in cutaneous disease: Part II

“…130 Cathelicidins are antimicrobial peptides that are believed to directly kill microorganisms, participate in the innate immune system, and form a chemical shield of protection on the skin. [130][131][132] LL-37 is the C-terminal part of the only human cathelicidin identified to date, called human cationic antimicrobial protein. 133,134 LL-37 is expressed by polymorphonuclear leukocytes, lymphocytes, macrophages, and epithelial cells.…”