Antimicrobial Peptides and Innate Immunity by Pieter S. Hiemstra & Sebastian A. J. Zaat

Author:Pieter S. Hiemstra & Sebastian A. J. Zaat
Language: eng
Format: epub
Publisher: Springer Basel, Basel

4 Antimicrobial Activity of ELR CXC Chemokines

4.1 Granulocyte Chemotactic Protein-2 (GCP-2)/CXCL6

Granulocyte chemotactic protein-2 (GCP-2)/CXCL6 is a chemokine of the ELR CXC family, made up of 77 amino acids residue (Proost et al. 1993a, b; Froyen et al. 1997; Van Damme et al. 1997). It is mainly involved in chemoattracting neutrophils (Froyen et al. 1997; Wuyts et al. 1997; Viola and Luster 2008) due to its interactions with the chemokine receptors CXCR1 and CXCR2 which are also expressed in monocytes and mast cells (Wuyts et al. 1997, 1998; Wolf et al. 1998). CXCL6 is expressed by epithelial cells, macrophages and mesenchymal cells (Fillmore et al. 2003; Collin et al. 2008; Mine et al. 2003; Prause et al. 2003; Gijsbers et al. 2004; Wuyts et al. 2003). CXCL6 has been shown to possess an important NaCl-sensitive antimicrobial activity (Collin et al. 2008), which is comparable with the activity of LL-37 (Linge et al. 2008b), a well-known human antimicrobial peptide of the cathelicidin family (Zanetti 2004). Gram-positive and Gram-negative bacteria that are normally involved in infections of dermis and mucosal surfaces are susceptible to the bactericidal action of CXCL6 (see Table 1), which appears to be related to the disruption of the bacterial membranes (Linge et al. 2008b). Interestingly, previous studies did not detect any antimicrobial activity of CXCL6 against E. coli and S. aureus (Yang et al. 2003). The discrepancies in the antibacterial activity can likely be attributed to the differences in the incubation media used in the different studies. Egesten and coworkers showed that under the same conditions, the antimicrobial activity of CXCL5/ENA-78 and CXCL7/NAP-2 against Streptococcus pyogenes was 30 times less than the activity of CXCL6 (Linge et al. 2008b). The structure of CXCL6 has not been determined yet, but a structural model can be predicted based on the known structures of other members of the CXC chemokine family, which showed that the structure resembles the general fold of chemokines. The N-terminal region is devoid of regular secondary structure and it contains two cysteine residues located at positions 12 and 14, which form disulfide bonds with the Cys residues at positions 38 and 54. The central region is formed by three antiparallel β-strands and the C-terminal region is a short α-helix. The cationic charge and amphipathicity of the C-terminal α-helix resembles the biochemical properties and secondary structure of some antimicrobial peptides, pinpointing this region of the chemokine as being possibly responsible for the antibacterial activity. Comparisons of the antimicrobial activity of the full-length CXCL6 protein and peptides resembling the N-terminal or C-terminal region of CXCL6 established that full-length CXCL6 is more active than either of these peptides. Interestingly, the bactericidal activity of the peptide encompassing the N-terminal region was higher than the activity of the C-terminal α-helix peptide, indicating that the C-terminal region alone is not the major determinant for the antimicrobial activity. Instead, the N-terminal region seems to be more relevant for the bactericidal activity in this case. These results also correlate with the higher leakage induced in DOPE/DOPG liposomes by CXCL6 and its N-terminal region peptide.

Download

Copyright Disclaimer:
This site does not store any files on its server. We only index and link to content provided by other sites. Please contact the content providers to delete copyright contents if any and email us, we'll remove relevant links or contents immediately.