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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.


Hsin-Ni Li

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


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.

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
Keywords cationic host defense peptide; antimicrobial peptide; innate immunity; inflammation; efferocytosis
Public URL
Publisher URL
Contract Date Jul 13, 2018


Secondary necrosis of apoptotic neutrophils... (875 Kb)

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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

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