Phospholipase A2-modified LDL is taken up at enhanced rate by macrophages.
Modification of the low density lipoprotein (LDL) core or surface lipids were shown to affect the cellular uptake of the lipoproteins and hence the formation of foam cell macrophages. In the present study phospholipase A2 treatment of LDL was shown to produce negatively charged lipoprotein with increased content of lysolechitine. This modified lipoprotein was taken up and degraded by J-774 A.1 macrophage-like cell line at enhanced rate (up to 97% when 10 units/ml of PLase A2 was used) in comparison to control LDL. This effect of PLase A2 was enzyme dose dependent. Competition experiments revealed that the uptake of PLase A2-LDL by the macrophages was specific and was mediated via the LDL receptor. Since PLase A2 was found to exist in various tissues, thus the production of PLase A2-LDL under certain pathological conditions can potentially contribute to foam cell formation and accelerated atherosclerosis.
Aviram
M
M
Lipid Research Laboratory, Rambam Medical Center, Rappaport Family Institute for Research in the Medical Sciences, Technion Faculty of Medicine, Haifa, Israel.
Maor
I
I
D000818:Animals; D004305:Dose-Response Relationship, Drug; D008077:Lipoproteins, LDL / Q000187:drug effects* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010741:Phospholipases A / Q000494:pharmacology*; D054467:Phospholipases A2; D011973:Receptors, LDL / Q000378:metabolism
D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D010741:Phospholipases A; D054467:Phospholipases A2