Hsin-Ni Li
Secondary necrosis of apoptotic neutrophils induced by the human cathelicidin LL-37 is not proinflammatory to phagocytosing macrophages
Li, Hsin-Ni; Barlow, Peter G.; Bylund, Johan; Mackellar, Annie; Bj�rstad, �se; Conlon, James; Hiemstra, Pieter S.; Haslett, Chris; Gray, Mohini; Simpson, A. John; Rossi, Adriano G.; Davidson, Donald J.
Authors
Prof Peter Barlow P.Barlow@napier.ac.uk
Professor
Johan Bylund
Annie Mackellar
�se Bj�rstad
James Conlon
Pieter S. Hiemstra
Chris Haslett
Mohini Gray
A. John Simpson
Adriano G. Rossi
Donald J. Davidson
Abstract
Cathelicidins are CHDP with essential roles in innate host defense but also more recently associated with the pathogenesis of certain chronic diseases. These peptides have microbicidal potential and the capacity to modulate innate immunity and inflammatory processes. PMN are key innate immune effector cells with pivotal roles in defense against infection. The appropriate regulation of PMN function, death, and clearance is critical to innate immunity, and dysregulation is implicated in disease pathogenesis. The efferocytosis of apoptotic PMN, in contrast to necrotic cells, is proposed to promote the resolution of inflammation. We demonstrate that the human cathelicidin LL-37 induced rapid secondary necrosis of apoptotic human PMN and identify an essential minimal region of LL-37 required for this activity. Using these LL-37-induced secondary necrotic PMN, we characterize the consequence for macrophage inflammatory responses. LL-37-induced secondary necrosis did not inhibit PMN ingestion by monocyte-derived macrophages and in contrast to expectation, was not proinflammatory. Furthermore, the anti-inflammatory effects of apoptotic PMN on activated macrophages were retained and even potentiated after LL-37-induced secondary necrosis. However, this process of secondary necrosis did induce the release of potentially harmful PMN granule contents. Thus, we suggest that LL-37 can be a potent inducer of PMN secondary necrosis during inflammation without promoting macrophage inflammation but may mediate host damage through PMN granule content release under chronic or dysregulated conditions.
Citation
Li, H.-N., Barlow, P. G., Bylund, J., Mackellar, A., Björstad, Å., Conlon, J., Hiemstra, P. S., Haslett, C., Gray, M., Simpson, A. J., Rossi, A. G., & Davidson, D. J. (2009). Secondary necrosis of apoptotic neutrophils induced by the human cathelicidin LL-37 is not proinflammatory to phagocytosing macrophages. Journal of Leukocyte Biology, 86(4), 891-902. https://doi.org/10.1189/jlb.0209050
Journal Article Type | Article |
---|---|
Acceptance Date | May 16, 2009 |
Online Publication Date | Jul 6, 2009 |
Publication Date | 2009-10 |
Deposit Date | Mar 27, 2012 |
Publicly Available Date | Jul 13, 2018 |
Journal | Journal of Leukocyte Biology |
Print ISSN | 0741-5400 |
Electronic ISSN | 1938-3673 |
Publisher | Society for Leukocyte Biology |
Peer Reviewed | Peer Reviewed |
Volume | 86 |
Issue | 4 |
Pages | 891-902 |
DOI | https://doi.org/10.1189/jlb.0209050 |
Keywords | cationic host defense peptide; antimicrobial peptide; innate immunity; inflammation; efferocytosis |
Public URL | http://researchrepository.napier.ac.uk/id/eprint/5178 |
Publisher URL | http://dx.doi.org/10.1189/jlb.0209050 |
Contract Date | Jul 13, 2018 |
Files
Secondary necrosis of apoptotic neutrophils...
(875 Kb)
PDF
Publisher Licence URL
http://creativecommons.org/licenses/by-nc/3.0/
Copyright Statement
© 2009 Society for Leukocyte Biology
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited
You might also like
Evolution and immunopathology of chikungunya virus informs therapeutic development
(2023)
Journal Article
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
(2021)
Journal Article