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Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
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
Doi: 10.1016/j.bbalip.2014.11.010
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Leading authors Med Uni Graz
- Curcic Sanja
- Marsche Gunther
- Co-authors Med Uni Graz
- Frei-Winterleitner Robert
- Heinemann Akos
- Holzer Michael
- Pasterk Lisa
- Schicho Rudolf
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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