Activated platelets secrete a protein-like factor that stimulates oxidized-LDL receptor activity in macrophages.
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.
Fuhrman
B
B
Lipid Research Unit, Rambam Medical Center, Haifa, Israel.
Brook
G J
GJ
Aviram
M
M
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D003470:Culture Media; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D010101:Oxygen Consumption; D015539:Platelet Activation; D011973:Receptors, LDL / Q000378:metabolism*
D001798:Blood Proteins; D003470:Culture Media; D011973:Receptors, LDL