Antimicrobial peptides cathelicidins

Hertting, O., Hohn, A., Luthje, P. et al. 2010. Vitamin D induction of the human antimicrobial peptide cathelicidin in the urinary bladder. PLoS One 5 el5580. 

Yamshchikov, A. V., Kurbatova, E. V., Kumari, M. et al. 2010. Vitamin D status and antimicrobial peptide cathelicidin (LL-37) concentrations in patients with active pulmonary tuberculosis. Am J Clin Nutr 92 603-11. 

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... 

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. 

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]. 

Although l,25(OH)2D3 obviously acts primarily by dampening on APCs, newer results indicate an active immunoprotective and especially antimicrobial role of l,25(OH)2D3 [91]. Activation of pathogen associated molecular patterns on macrophages such as Toll-like receptor (TLR) 2 leads to VDR expression and to local synthesis of l,25(OH)2D3. This in turn induced expression of cathelicidin, an antimicrobial peptide of the skin [92], Vice versa, VDR ligation may increase TLR2 expression on keratinocytes and thereby complement expression of cathelicidin [93]. 

Sigurdadottir T, Andersson P, Davoudi M, Malmsten M, Schmidtchen A, Bodelsson M. In silico identification and biological evaluation of antimicrobial peptides based on human cathelicidin LL-37. Antimicrob Agents Chemother 2006 50 2983-9. 

Durr UH, Sudheendra US, Ramamoorthy A. LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochim Biophys Acta 2006 1758 1408-25. 

Andrushchenko VV, Vogel HJ, Prenner EJ. Interactions of tryptophan-rich cathelicidin antimicrobial peptides with model membranes studied by differential scanning calorimetry. Biochim Biophys Acta 2007 1768 2447-58. 

Zhu WL, Hahm KS, Shin SY (2007) Cathelicidin-derived Trp/Pro-rich antimicrobial peptides with lysine peptoid residue (nlys) therapeutic index and plausible mode of action. J Pept Sci 13 529-535... 

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 presumed mechanism of anti-TB activity is the local macrophage production of cathelicidin (LL-37), a highly specific antimicrobial protein (peptide) whose synthesis is stimulated by intracellular 25(OH)2D (Adams 2006). 

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