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Research Article Free access | 10.1172/JCI116413

Phospholipase D-modified low density lipoprotein is taken up by macrophages at increased rate. A possible role for phosphatidic acid.

M Aviram and I Maor

Lipid Research Laboratory, Rambam Medical Center, Haifa, Israel.

Find articles by Aviram, M. in: PubMed | Google Scholar

Lipid Research Laboratory, Rambam Medical Center, Haifa, Israel.

Find articles by Maor, I. in: PubMed | Google Scholar

Published May 1, 1993 - More info

Published in Volume 91, Issue 5 on May 1, 1993
J Clin Invest. 1993;91(5):1942–1952. https://doi.org/10.1172/JCI116413.
© 1993 The American Society for Clinical Investigation
Published May 1, 1993 - Version history
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Abstract

Macrophage uptake of modified forms of LDL leads to cellular cholesterol accumulation. Upon incubation of LDL with phospholipase D (PLase D), a time- and enzyme dose-dependent production of phosphatidic acid (PA), paralleled by a rapid reduction in LDL phosphatidyl choline content (up to 65% within 15 min of incubation) was noted. No lipid peroxidation could be found in PLase D-modified LDL. Upon in vitro incubation of PLase D-LDL with copper ions, however, this modified LDL was substantially oxidized. The addition of 100 micrograms PA/ml to native LDL for the period of its in vitro oxidation resulted in a 63% elevation in the lipoprotein peroxides content. Incubation of PLase D-LDL with J-774A.1 macrophage-like cell line resulted in an increase in its cellular binding and degradation (up to 91 and 110%, respectively) in comparison with native LDL (via the LDL receptor). When PA was added to LDL before its incubation with the macrophages, a PA dose-dependent elevation in the cellular uptake of LDL (by up to twofold) was noted in comparison with LDL that was incubated without PA, suggesting that PA production in PLase D-LDL may be involved in the increased cellular uptake of PLase D-LDL. PLase D activity towards LDL was demonstrated in J-774A.1 macrophages. Human plasma was also shown to possess PLase D activity. Thus, PLase D modification of LDL may take place under certain pathological conditions and PLase D-LDL interaction with arterial wall macrophages can potentially lead to foam cell formation.

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