Activated platelets secrete a protein-like factor that stimulates oxidized-LDL receptor activity in macrophages.

• Main Authors: B Fuhrman, GJ Brook, M Aviram
• Format: Article
• Language: English
• Published: Elsevier 1991-07-01
• Series: Journal of Lipid Research
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520419741

Platelet secretory products were shown to modulate the interaction between lipoproteins and their receptors on macrophages. Preincubation of macrophages for 2 h at 37 degrees C with platelet conditioned medium (PCM), followed by its removal and a further 5-h incubation in the presence of oxidized-LDL (Ox-LDL), resulted in increased cellular degradation of Ox-LDL (34%), stimulation of cellular cholesterol esterification (31%), and mass accumulation of esterified and nonesterified cholesterol (25% and 41%, respectively). These effects were found to be the result of a PCM-mediated increase in the number of Ox-LDL receptors on macrophages. PCM was shown to interact with the macrophage scavenger receptor. Enhanced Ox-LDL uptake by macrophages preincubated with PCM could not be reproduced when PCM remained in the incubation medium. Maintenance of PCM in the incubation medium reduced Ox-LDL uptake by macrophages (40%) and was shown to be PCM dose-dependent. Whereas incubation at 37 degrees C demonstrated enhanced uptake of Ox-LDL, preincubation of macrophages with PCM at 4 degrees C exhibited a 64% reduction in Ox-LDL-mediated cellular cholesterol esterification. Thus, PCM internalization by macrophages after its binding to the scavenger receptor is required to promote the enhancing effect of PCM on Ox-LDL uptake by macrophages. PCM activity was associated with platelet degranulation, and was recovered in the protein fraction of PCM. It was found to be heat- and trypsin-labile with a molecular weight greater than 25,000. PCM obtained from platelets derived from a patient with alpha granules deficiency failed to enhance the uptake of Ox-LDL by macrophages, suggesting that the active protein-like factor in PCM originated from platelet alpha granules. These results indicate that a platelet-secreted protein-like factor can modulate macrophage uptake of Ox-LDL with subsequent effect on foam cell formation.