Cathelicidins

Howell MD The role of human p defensins and cathelicidins in atopic dermatitis. Curr Opin Allergy Clin Immunol 2007 7 413-417. 

In mammals, two groups of host defense peptides are prominent the cathelicidins (notably human LL-37, porcine protegrin, and bovine indolicidin) and the defensins (human a- and /3-defensins). These two classes of peptides are involved in both intracellular and extracellular defensive responses and as individual peptides can be synthesized and stored in either active or inactive form within cells or secreted through degranulation into the surrounding environment. ... 

Figure 1 Cartoon representation of the human cathelicidin hCAPI 8. The amino acid residues that define each of the three hCAP18 domains have been added. The sequence of LL-37, the host defense peptide derived from hCAP18, is found in the inset. Structure-activity relationship studies have identified regions within the peptide that are necessary for both antimicrobial and immunomodulatory activities.

In addition to the cathelicidins and defensins, humans also utilize a variety of other host defense peptides. Examples of these include the anionic dermcidins, found in human sweat and possessing potent antimicrobial activity in a broad range of pH and salt concentrations, and the histatins, a histidine-rich host defense peptide family found in humans and higher primate species. The histatins are normally found in saliva and utilize an alternative mechanism to bacterial membrane lysis for their antimicrobial activity. ... 

The amphipathic a-helical class of host defense peptides is the most abundant and most well-characterized class. Upon interaction with the hydrophobic membrane environment, the largely unstructured peptide adopts an amphipathic ct-helical conformation with one helical face containing the majority of the hydrophobic residues, the opposite containing a large proportion of the polar residues. These peptides are often short (<40 amino acids), devoid of cysteine residues, and found to be unstructured or linear in nonhydrophobic environments. Peptides found within this class include the antimicrobial peptide alamethicin, bee venom melittin, the magainins, and the human cathelicidin LL-37. ... 

Shinnar AE, Butler KL, Park HJ (2003) Cathelicidin Family of Antimicrobial Peptides Proteolytic Processing and Protease Resistance. Bioorg Chem 31 425... 

Yang, D., Biragyn, A., Hoover, D.M., Lubkowski, J. and Oppenheim, JJ. (2004) Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Atom. Rev. Immunol. 22, 181-215. 

Dorschner, R.A., Pestonjamasp, V.K., Tamakuwala, S et al. (2001) Cutaneous injury induces the release of cathelicidin anti-microbial peptides active against group A streptococcus. J. Invest. Dermatol. 117, 91-97. 

Tossi, A., Scocchi, M., Zanetti, M., Gennaro, R., Storici, P. and Romeo, D. (1997) An approach combining rapid cDNA amplification and chemical synthesis for the identification of novel, cathelicidin-derived, antimicrobial peptides. Methods Mol. Biol. 78, 133-150. 

Spinigerin in H20/TFE 10% -Conotoxin [K10]MVIIA Fowlicidin-1, a novel cathelicidin AMP from chicken spiniger P. spiniger... 

These last factors also up-regulate hBD-2 secretion by the intestinal epithelial cell lineage Caco-2 stimulated with probiotic bacteria [176]. Although not yet demonstrated experimentally, mammalian cathelicidins may respond to inflammatory stimuli, since the 5 flanking sequences upstream of the peptide coding sequence have several potential consensus sequences for transcription factors involved in inflammatory response, sueh as NF-kB, NF-IL-6, acute-phase response factor and IFN-y response elements [147,170,177]. 

Cathelicidins and defensins induce histamine release from mast cells [182-184]. Human BD-2, -3 and -4 and a-defensins recruit monocytes, T cells (memory and naive) and immature dendritic cells [185-188] Cathelicidins (bovine, human, mouse and pig) are chemotactic for several subsets of peripheral blood cells in vitro [178,189] and in vivo [190]. For example, CRAMP (Cathelin-related antimicrobial peptide, the murine orthologue of human cathelicidin/LL-37), like LL-37, was chemotactic for human monocytes, neutrophils, macrophages, and for mouse peripheral blood leukocytes in vitro and in vivo [189]. These results suggest that host defense peptides recruit innate and adaptive immune cells for protective cellular and humoral responses to pathogens. 

Cathelicidins may also control tissue damage and inflammation, inhibiting the production of reactive oxygen species (proline-arginine-rich porcine cathelicidin, PR-39) or inducing apoptosis in activated lymphocytes (bovine antimicrobial peptide-28) [9]. 

Resolution of inflammatory processes is completed by tissue regeneration, and cathelicidins and defensins also promote cell proliferation [197,198], angiogenesis [159] and wound repair [199]. 

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