Mk. Cathcart et al., LIPOPROTEIN RECEPTOR INTERACTIONS ARE NOT REQUIRED FOR MONOCYTE OXIDATION OF LDL, Journal of lipid research, 36(9), 1995, pp. 1857-1865
Upon activation, human peripheral blood monocytes and U937 cells oxidi
zed low density lipoprotein (LDL), converting it to a cytotoxin. The o
xidized LDL loses its ability to interact specifically with the native
LDL (apoB/E) receptor and becomes a ligand for the scavenger receptor
s and two other receptors, Fc gamma RII (CD32) and CD36. We performed
a series of studies to evaluate the potential contribution of each of
these receptors to the process of monocyte-mediated LDL oxidation. To
assess the participation of the apoB/E receptor, we tested the ability
of activated human monocytes to oxidize LDL after up- and down-regula
tion of apoB/E receptors. Neither up-regulation nor down-regulation of
the apoB/E receptor significantly modified the level of LDL lipid oxi
dation. Acetylated LDL, a ligand for scavenger receptors, was also oxi
dized by the activated monocytes. Methylated LDL, a chemically modifie
d LDL that is not recognized by the apoB/E or scavenger receptors, was
oxidized as well. Thus, LDL does not need to interact with either the
apoB/E receptor or scavenger receptors in order to undergo lipid oxid
ation. Additionally, monoclonal antibodies to CD36 and CD32 were used
to block these two receptors that recognize oxidized LDL. Although bot
h antibodies interfered with oxidized LDL binding to these receptors,
neither treatment interfered with LDL lipid oxidation mediated by acti
vated human monocytes. Our results suggest that interaction with these
receptors is not a requirement for LDL lipid oxidation by activated h
uman monocytes.