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• W2044487577 abstract "Secretory phospholipase A 2 (sPLA 2 ) generates bioactive lysophospholipids implicated in acute and chronic inflammation, but the pathophysiologic role of sPLA 2 is poorly understood. Given that high-density lipoprotein (HDL) is the major substrate for sPLA 2 in plasma, we investigated the effects of sPLA 2 -mediated modification of HDL (sPLA 2 -HDL) on neutrophil function, an essential arm of the innate immune response and atherosclerosis. Treatment of neutrophils with sPLA 2 -HDL rapidly prevented agonist-induced neutrophil activation, including shape change, neutrophil extracellular trap formation, CD11b activation, adhesion under flow and migration of neutrophils. The cholesterol-mobilizing activity of sPLA 2 -HDL was markedly increased when compared to native HDL, promoting a significant reduction of cholesterol-rich signaling microdomains integral to cellular signaling pathways. Moreover, sPLA 2 -HDL effectively suppressed agonist-induced rise in intracellular Ca 2 + levels. Native HDL showed no significant effects and removing lysophospholipids from sPLA 2 -HDL abolished all anti-inflammatory activities. Overall, our studies suggest that the increased cholesterol-mobilizing activity of sPLA 2 -HDL and suppression of rise in intracellular Ca 2 + levels are likely mechanism that counteracts agonist-induced activation of neutrophils. These counterintuitive findings imply that neutrophil trafficking and effector responses are altered by sPLA 2 -HDL during inflammatory conditions. • sPLA 2 modified HDL suppresses neutrophil activation in response to several agonists. • sPLA 2 modification markedly improves cholesterol mobilizing activity of HDL. • sPLA 2 -HDL promotes a significant reduction of cholesterol-rich lipid rafts. • sPLA 2 -HDL effectively suppresses agonist-induced rise in intracellular Ca 2 + levels. • Lysophospholipid content of sPLA 2 -HDL mediates anti-inflammatory effects." @default.
• W2044487577 created "2016-06-24" @default.
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• W2044487577 date "2015-02-01" @default.
• W2044487577 modified "2023-10-12" @default.
• W2044487577 title "Neutrophil effector responses are suppressed by secretory phospholipase A2 modified HDL" @default.
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• W2044487577 doi "https://doi.org/10.1016/j.bbalip.2014.11.010" @default.
• W2044487577 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4789498" @default.
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