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* Centre d’Etude et de Recherche en Virologie et Immunologie, Institut National de la Santé et de la Recherche Médicale, Lyon, France; and
Unité Mixte de Recherche, Centre National de la Recherche Scientifique-bioMérieux SA, Ecole Normale Supérieure de Lyon, Lyon, France
During the acute phase response, the interplay between high density
lipoproteins and low density lipoproteins (LDL) favors transient
generation of oxidized LDL with proinflammatory activities. We
hypothesized that oxidative modification of LDL is an endogenous signal
for the immune system, and we have shown that oxidized LDL promotes
mature dendritic cell transition from monocyte, therefore linking the
nonspecific acute phase response to adaptive immunity.
Lysophosphatidylcholine (LPC) is a major lipid component of oxidized
LDL with reported proinflammatory activities. We now report that LPC
acts through G protein-coupled receptors on differentiating monocytes
to generate mature dendritic cells with the ability to stimulate IL-2
and IFN-
production by allogeneic T lymphocytes. LPC is most
effective in lipoprotein-deprived serum and can be inhibited by an
excess of native LDLs reflecting normal plasma conditions. Therefore,
by controlling the balance between native and oxidized lipoproteins and
the resulting production of LPC, the acute phase reactants may provide
a context of Ag presentation that is transiently favorable to immune
activation. Intralipid, a therapeutic lipid emulsion for parenteral
nutrition with unexplained immunomodulatory properties, also blocked
LPC activity. This opens perspectives for the understanding and
treatment of acute and chronic inflammatory
diseases.
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