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• W2583111036 startingPage "146" @default.
• W2583111036 abstract "The protection exerted by neutrophils against invading microbes is partially mediated via the generation of neutrophil extracellular traps (NETs). In sterile conditions NETs are damaging species, enriched in autoantigens and endowed with the ability to damage the vessel wall and bystander tissues, to promote thrombogenesis, and to impair wound healing. To identify and reposition agents that can be used to modulate the formation of NETs is a priority in the research agenda. Low molecular weight heparins (LMWH) are currently used, mostly on an empirical basis, in conditions in which NETs play a critical role, such as pregnancy complications associated to autoimmune disease. Here we report that LMWHs induce a profound change in the ability of human neutrophils to generate NETs and to mobilize the content of the primary granules in response to unrelated inflammatory stimuli, such as IL-8, PMA and HMGB1. Autophagy consistently accompanies NET generation in our system and autophagy inhibitors, 3-MA and wortmannin, prevent NET generation. Pretreatment with LMWH in vitro critically jeopardizes neutrophil ability to activate autophagy, a mechanism that might contribute to neutrophil unresponsiveness. Finally, we verified that treatment of healthy volunteers with a single prophylactic dose of parnaparin abrogated the ability of neutrophils to activate autophagy and to generate NETs. Together, these results support the contention that neutrophils, and NET generation in particular, might represent a preferential target of the anti-inflammatory action of LMWH." @default.
• W2583111036 created "2017-02-10" @default.
• W2583111036 creator A5016278352 @default.
• W2583111036 creator A5047988727 @default.
• W2583111036 creator A5060924409 @default.
• W2583111036 creator A5087520444 @default.
• W2583111036 date "2017-09-01" @default.
• W2583111036 modified "2023-10-02" @default.
• W2583111036 title "Low molecular weight heparins prevent the induction of autophagy of activated neutrophils and the formation of neutrophil extracellular traps" @default.
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• W2583111036 doi "https://doi.org/10.1016/j.phrs.2016.08.008" @default.
• W2583111036 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28161237" @default.
• W2583111036 hasPublicationYear "2017" @default.
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