Document Detail


Hypersusceptibility of neutrophil granulocytes towards lethal action of free fatty acids contained in enzyme-modified atherogenic low density lipoprotein.
MedLine Citation:
PMID:  19423111     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The bulk of LDL entrapped in the arterial intima is modified by hydrolytic enzymes, leading to extensive cleavage of cholesterylesters and liberation of fatty acids. The latter induce apoptosis in endothelial cells but are far less cytotoxic towards macrophages. We have compared the cytotoxic effects of enzymatically modified LDL (E-LDL) on macrophages and polymorphonuclear granulocytes (PMN). METHODS AND RESULTS: E-LDL displayed toxicity towards PMN at far lower concentrations than towards monocyte-derived macrophages. Native or oxidized LDL had no effect. Free fatty acids contained in E-LDL were the cause of the observed toxicity, which could be mimicked by linoleic acid, oleic acid and arachidonic acid. E-LDL provoked Ca(2+) influx and activated PMN, as witnessed by the generation of superoxide anions and peroxidase secretion. Inhibition of either oxidative burst or calcium influx did not diminish the cytotoxicity of E-LDL. Similar to free linoleic acid, E-LDL lysed red blood cells and rapidly rendered cells permeable to propidium iodide. CONCLUSION: Possibly through their capacity to directly perturb cell membranes, free fatty acids contained in E-LDL exert potent cytotoxic effects on PMN. This may be one reason why PMN are not abundantly present in atherosclerotic lesions, and why PMN-depletion suppresses atherogenesis.
Authors:
Cornelia Aquilina Lux; Andreas Koschinski; Katrin Dersch; Matthias Husmann; Sucharit Bhakdi
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-04-11
Journal Detail:
Title:  Atherosclerosis     Volume:  207     ISSN:  1879-1484     ISO Abbreviation:  Atherosclerosis     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-09     Completed Date:  2010-01-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  116-22     Citation Subset:  IM    
Affiliation:
Institute of Medical Microbiology and Hygiene, Johannes Gutenberg-University Mainz, Hochhaus am Augustusplatz, 55131 Mainz, Germany.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Animals
Arachidonic Acid / metabolism
Atherosclerosis / metabolism*,  pathology
Calcium / metabolism
Cell Death
Cell Membrane Permeability
Cell Survival
Cells, Cultured
Fatty Acids, Nonesterified / metabolism*
Hemolysis
Humans
Hydrolysis
L-Lactate Dehydrogenase / metabolism
Linoleic Acid / metabolism
Lipoproteins, LDL / metabolism*
Macrophages / metabolism*,  pathology
Neutrophils / metabolism*,  pathology
Oleic Acid / metabolism
Peptide Hydrolases / metabolism*
Peroxidase / metabolism
Rabbits
Respiratory Burst
Sterol Esterase / metabolism*
Superoxides / metabolism
Time Factors
Chemical
Reg. No./Substance:
0/Fatty Acids, Nonesterified; 0/Lipoproteins, LDL; 0/oxidized low density lipoprotein; 11062-77-4/Superoxides; 112-80-1/Oleic Acid; 2197-37-7/Linoleic Acid; 506-32-1/Arachidonic Acid; 56-65-5/Adenosine Triphosphate; 7440-70-2/Calcium; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 1.11.1.7/Peroxidase; EC 3.1.1.13/Sterol Esterase; EC 3.4.-/Peptide Hydrolases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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