2016
DOI: 10.4049/jimmunol.1600051
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Neutrophil Necroptosis Is Triggered by Ligation of Adhesion Molecules following GM-CSF Priming

Abstract: Apoptosis is the most common form of neutrophil death under both physiological and inflammatory conditions. However, forms of nonapoptotic neutrophil death have also been observed. In the current study, we report that human neutrophils undergo necroptosis after exposure to GM-CSF followed by the ligation of adhesion receptors such as CD44, CD11b, CD18, or CD15. Using a pharmacological approach, we demonstrate the presence of a receptor-interacting protein kinase-3 (RIPK3)-a mixed lineage kinase-like (MLKL) sig… Show more

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Cited by 72 publications
(104 citation statements)
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“…To this end, we examined the role of necroptosis in an A. fumigatus extract ( Asp . )‐induced allergic airway inflammation, using a recently discovered murine necroptosis inhibitor, GW80 . Treatment with GW80 resulted in delayed cell death kinetics for TSZ‐, but not TS‐, treated IL‐33‐GFP‐expressing L929 or HaCaT cells, thus confirming its ability to inhibit necroptotic cell death in vitro (Fig.…”
Section: Resultsmentioning
confidence: 62%
“…To this end, we examined the role of necroptosis in an A. fumigatus extract ( Asp . )‐induced allergic airway inflammation, using a recently discovered murine necroptosis inhibitor, GW80 . Treatment with GW80 resulted in delayed cell death kinetics for TSZ‐, but not TS‐, treated IL‐33‐GFP‐expressing L929 or HaCaT cells, thus confirming its ability to inhibit necroptotic cell death in vitro (Fig.…”
Section: Resultsmentioning
confidence: 62%
“…This necroptosis is coordinated by RIPK1, RIPK3, and MLKL, which finally results in a compromised membrane integrity and the release of cytosolic components 20 . Necroptosis can be triggered by engagement of CD44, CD11b, CD18, or CD15 on GM-CSF-primed neutrophils 21 or by autophagy 22 .…”
Section: Ways Of Neutrophilic Cell Deathmentioning
confidence: 99%
“…If the source of infection/stimulation persists, the released mtDNA, having similarity to viral and bacterial DNA (enriched in unmethylated CpG motifs), acts as a danger signal and triggers cytokine production for a protective and regulated immune response 7,55 . b Cytolysis: Under pathological conditions, such as the persistent presence of foreign antigens 104 , "too large to be trapped antigens", such as fungal hyphae 60,61 , strong adhesion receptor activation [153][154][155] , presence of monosodium urate (MSU) 88 , or phorbol-myristate-acetate (PMA) stimulation 2,12 , results in an excess of reactive oxygen species (ROS), leading to neutrophil cytolysis. Similarly, excessive increases in intracellular calcium [Ca 2+ ] i by ionomycin results in non-apoptotic neutrophil death 12,81 .…”
Section: Nets and Eets In Bacterial Infectionsmentioning
confidence: 99%