| 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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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
Previous Document: Effect of losartan on ambulatory short-term blood pressure variability and cardiovascular remodeling...
Next Document: Association of serum osteoprotegerin with ankle-brachial index and urine albumin: Creatinine ratio i...