The human lactoferrin-derived peptide hLF1-11 exerts immunomodulatory effects by specific inhibition of myeloperoxidase activity.

Abstract

Because of their ability to eliminate pathogens and to modulate various host immune responses, antimicrobial peptides are considered as candidate agents to fight infections by (antibiotic-resistant) pathogens. We recently reported that hLF1-11 (GRRRRSVQWCA), an antimicrobial peptide derived from the N terminus of human lactoferrin, displays diverse modulatory activities on monocytes, thereby enhancing their actions in innate immune responses. The aim of this study was to identify the cellular target of hLF1-11 that mediates these effects. Results revealed that hLF1-11 binds and subsequently penetrates human monocytes, after which it inhibits the enzymatic activities of myeloperoxidase (MPO). Moreover, a chemical inhibitor of MPO (aminobenzoic acid hydrazide) mimicked the effects of hLF1-11 on the inflammatory response by monocytes and on monocyte-macrophage differentiation. Computer-assisted molecular modeling predicted that hLF1-11 can bind to the edge of and within the crevice of the active site of MPO. Experiments with a set of hLF1-11 peptides with amino acid substitutions identified the stretch of arginines and the cysteine at position 10 as pivotal in these immunomodulatory properties of hLF1-11. We conclude that hLF1-11 may exert its modulatory effects on human monocytes by specific inhibition of MPO activity.

• Authors: Anne M van der Does, Paul J Hensbergen, Sylvia J Bogaards, Medine Cansoy, André M Deelder, Hans C van Leeuwen, Jan W Drijfhout, Jaap T van Dissel, Peter H Nibbering
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 188 Issue 10 Pg. 5012-9 (May 15 2012) ISSN: 1550-6606 [Electronic] United States
• PMID: 22523385 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Immunologic Factors
• Peroxidase
• Lactoferrin

Topics

• Anti-Bacterial Agents
• Cells, Cultured
• Humans
• Immunologic Factors (physiology)
• Lactoferrin (physiology)
• Monocytes (enzymology, immunology)
• Peroxidase (antagonists & inhibitors, metabolism)