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Neutrophil secondary necrosis is induced by LL‐37 derived from cathelicidin
Author(s) -
Zhang Zhifang,
Cherryholmes Gregory,
Shively John E.
Publication year - 2008
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0208086
Subject(s) - biology , apoptosis , cathelicidin , propidium iodide , granulocyte , tumor necrosis factor alpha , necrosis , neutrophil extracellular traps , annexin , chemotaxis , immunology , innate immune system , microbiology and biotechnology , inflammation , programmed cell death , immune system , biochemistry , receptor , genetics
Neutrophils represent the most common granulocyte subtype present in blood. The short half‐life of circulating neutrophils is regulated by spontaneous apoptosis, and tissue infiltrating neutrophils die by apoptosis and secondary necrosis. The mechanism of neutrophil apoptosis has been the subject of many studies; however, the mechanism of neutrophil secondary necrosis is less clear. Human cathelicidin cationic peptide 18, proteolytically processed to its active form, LL‐37, is secreted by neutrophils and epithelial cells and shown to have effects in addition to bacterial lysis. We demonstrate here that LL‐37 affects neutrophil lifespan by the pathway of secondary necrosis, rapidly converting annexin V‐positive (AV + ), propidium iodide‐negative (PI − ; apoptotic) cells into PI + (necrotic) cells with the release of IL‐8, IL‐1R antagonist, ATP, and intact granules. The effects of LL‐37 on apoptotic neutrophils are neither energy‐dependent nor affected by pretreatment with G‐CSF, GM‐CSF, TNF‐α, and LPS and are partially inhibited by human serum. Moreover, LL‐37 decreases CXCR2 expression of AV − PI − (live) neutrophils, suggesting an effect on the neutrophil response to its chemotactic factors, including IL‐8. Thus, the lifespan and inflammatory functions of neutrophils are directly affected by LL‐37.