| authors | Dijk, Albert van; Molhoek, E.M.; Veldhuizen, E.J.A.; Tjeerdsma-van Bokhoven, J.L.M.; Wagendorp, Eveline; Bikker, Floris; Haagsman, H.P. |
| source | Molecular immunology, Volume: 46 (2009), pp. 2465-2473 |
| full text | The full text of this item is not available due to the copyrights policy of the publisher.
|
| publisher | Elsevier |
| URL publisher | [Website publisher]
|
| document type | Article |
| version | Publisher version |
| disciplines | Diergeneeskunde |
| abstract | Chicken host defense peptide cathelicidin-2 (CATH-2) is known to exert antimicrobial and immunomodulatory
activities and consists of two -helices connected by a hinge region. Herewe report the biological
properties of the separate -helical segments and the importance of the proline residue in the hinge
region. Substitution of proline-14 in the CATH-2 hinge region by leucine, but not by glycine, strongly
reduced antibacterial and hemolytic activity. Furthermore, substitution by leucine strongly reduced the
neutralization of LPS-induced cytokine production and peptide-induced monocyte chemotactic protein-
1 (MCP-1) production by human peripheral blood mononuclear cells (PBMCs). This indicates that the
hinge region is important for rapid penetration of the bacterial membrane as well as indirect and direct
immunomodulatory activities. The highly cationic and amphipathic N-terminal segment (C1-15) exhibited
very potent antibacterial activity and fast killing kinetics, while displaying low cytotoxicity towards
chicken erythrocytes and PBMCs. The N-terminal and, to a lesser extent, the C-terminal helical regions
potently neutralized LPS-induced release of TNF , IL-6 and IL-10 by PBMCs, while IL-8 production was
only moderately affected. These results indicate that core elements within mature CATH-2 can be identified
that are linked to antibacterial and/or immunomodulatory activities. Further studies may lead to
the development of peptide antibiotics with specific properties that can be used for prophylactic and/or
therapeutic applications. |
| keywords | Host defense peptide, Cathelicidin, Innate immunity, Antibacterial activity |
| ISSN | 0161-5890 |
