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SHR Neuro Krebs Kardio Lipid

Curcic, S; Holzer, M; Frei, R; Pasterk, L; Schicho, R; Heinemann, A; Marsche, G.
Neutrophil effector responses are suppressed by secretory phospholipase A2 modified HDL.
Biochim Biophys Acta. 2015; 1851(2):184-193 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Curcic Sanja
Frei-Winterleitner Robert
Heinemann Akos
Holzer Michael
Marsche Gunther
Pasterk Lisa
Schicho Rudolf
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Number of Figures: 7
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Abstract:
Secretory phospholipase A2 (sPLA2) generates bioactive lysophospholipids implicated in acute and chronic inflammation, but the pathophysiologic role of sPLA2 is poorly understood. Given that high-density lipoprotein (HDL) is the major substrate for sPLA2 in plasma, we investigated the effects of sPLA2-mediated modification of HDL (sPLA2-HDL) on neutrophil function, an essential arm of the innate immune response and atherosclerosis. Treatment of neutrophils with sPLA2-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 sPLA2-HDL was markedly increased when compared to native HDL, promoting a significant reduction of cholesterol-rich signaling microdomains integral to cellular signaling pathways. Moreover, sPLA2-HDL effectively suppressed agonist-induced rise in intracellular Ca²⁺ levels. Native HDL showed no significant effects and removing lysophospholipids from sPLA2-HDL abolished all anti-inflammatory activities. Overall, our studies suggest that the increased cholesterol-mobilizing activity of sPLA2-HDL and suppression of rise in intracellular Ca²⁺ levels are likely mechanism that counteracts agonist-induced activation of neutrophils. These counterintuitive findings imply that neutrophil trafficking and effector responses are altered by sPLA2-HDL during inflammatory conditions. Copyright © 2014 Elsevier B.V. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
CD11b Antigen - metabolism
Calcium - metabolism
Calcium Signaling -
Cell Adhesion -
Cell Shape -
Cells, Cultured -
Chemotaxis, Leukocyte -
Cholesterol, HDL - metabolism
Extracellular Traps - metabolism
Humans -
Immunity, Innate -
Immunologic Factors - pharmacology
Lysophosphatidylcholines - metabolism
Neutrophil Activation - drug effects
Neutrophils - drug effects
Neutrophils - enzymology
Neutrophils - immunology
Phospholipases A2, Secretory - metabolism
Protein Processing, Post-Translational -
Signal Transduction - drug effects
Time Factors -

Find related publications in this database (Keywords)
HDL
Secretory phospholipase A(2)
Lysophospholipid
Neutrophil
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