Mature dendritic cell generation promoted by lysophosphatidylcholine.
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-gamma 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.
Coutant
Frédéric
F
Centre d'Etude et de Recherche en Virologie et Immunologie, Institut National de la Santé et de la Recherche Médicale, Lyon, France. lotteau@cervi-lyon.inserm.fr
Perrin-Cocon
Laure
L
Agaugué
Sophie
S
Delair
Thierry
T
André
Patrice
P
Lotteau
Vincent
V
D000210:Acute-Phase Reaction / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D051940:B7-2 Antigen; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology
D015703:Antigens, CD; D051940:B7-2 Antigen; C497964:CD86 protein, human; D005217:Fat Emulsions, Intravenous; D018836:Inflammation Mediators; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; C099252:oxidized low density lipoprotein; D019204:GTP-Binding Proteins