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Published on: November 10, 2017
Lipid-protein particles secreted from activated platelets reduce macrophage uptake of low density lipoprotein
Insights
Activated platelets release a particle that reduces low-density lipoprotein (LDL) uptake by macrophages. This process involves the scavenger receptor and inhibits cholesterol accumulation, suggesting a role for platelet-derived lipids in macrophage cholesterol regulation.
Area of Science:
- Biochemistry
- Cell Biology
- Immunology
Background:
- Low-density lipoprotein (LDL) uptake by macrophages is crucial for cholesterol homeostasis.
- Platelets play a role in various physiological and pathological processes, including inflammation and lipid metabolism.
Purpose of the Study:
- To investigate the effect of activated platelet conditioned medium (PCM) on macrophage LDL uptake.
- To identify the component in PCM responsible for inhibiting LDL uptake and cholesterol accumulation.
Main Methods:
- Macrophages were preincubated with PCM from activated platelets.
- LDL-mediated cholesterol accumulation and esterification were measured.
- LDL receptor activity was assessed.
- PCM was fractionated and delipidated to identify the active component.
- Experiments were conducted using U937 macrophages lacking scavenger receptors.
Main Results:
- PCM reduced cellular LDL uptake by 30-40% and inhibited LDL-mediated cholesterol accumulation and esterification in macrophages.
- The inhibitory effect was dose-dependent and linked to a reduction in LDL receptor number (apparent Vmax decreased by 35%).
- The active component was a lipid fraction of PCM (molecular weight >25,000 Da) that was taken up via the scavenger receptor, essential for reducing LDL receptor activity.
Conclusions:
- Activated platelets secrete a lipoprotein-like particle recognized by macrophage scavenger receptors.
- This interaction leads to reduced cellular LDL uptake, primarily due to the lipid constituents of the particle.
- Platelet-derived lipids may influence macrophage cholesterol metabolism through scavenger receptor-mediated pathways.
Abstract:
Cellular uptake of low density lipoprotein (LDL) was reduced by 30-40% in macrophages that were preincubated with platelet conditioned medium (PCM) obtained from activated platelets. LDL mediated cholesterol accumulation and cholesterol esterification in macrophages were substantially inhibited by macrophages preincubation with PCM. This inhibitory effect was found to be dose dependent, and resulted from a reduction in the number of LDL receptors (decrement of 35% in "apparent Vmax"). The active component in PCM was present only in medium obtained from activated platelets and was found to be of a molecular weight higher than 25,000 dalton. It comprised of both protein and cholesterol but upon PCM delipidation only the lipid fraction demonstrated the inhibitory effect on macrophage uptake of LDL. Specific uptake of the PCM lipoprotein-like particle via the scavenger receptor on macrophages was found to be essential for the expression of LDL receptor reduced activity. Furthermore, LDL mediated cholesterol esterification was not inhibited by PCM in U937 macrophages, a cell line that lacks the scavenger receptors. It is concluded that activated platelets secrete a lipoprotein-like particle which is recognized by the macrophage scavenger receptor. Subsequent to PCM-macrophage interaction, cellular LDL uptake was reduced. This effect could be attributed to the PCM lipid constituents.
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