title: Human group X secreted phospholipase A2 induces dendritic cell maturation through lipoprotein-dependent and -independent mechanisms.
abstract: OBJECTIVE
  Increased secreted phospholipase A(2) (sPLA(2)) activity has been documented in several inflammatory disorders. Among sPLA(2)s, the human group X (hGX)-sPLA(2) has the highest catalytic activity towards phosphatidylcholine (PC), the major phospholipid of cell membranes and blood lipoproteins. hGX-sPLA(2) has been detected in human atherosclerotic lesions, indicating that sPLA(2)s are an important link between lipids and inflammation, both involved in atherosclerosis. The presence of dendritic cells (DC), the most potent antigen presenting cells, in atherosclerotic lesions has raised the question about their role in disease progression.
  
  
  RESULTS
  In this study, we show that hGX-sPLA(2)-treated LDL induces human monocyte-derived DC maturation, resulting in a characteristic mature DC phenotype and enhanced DC ability to activate IFNγ secretion from T cells. hGX-sPLA(2) phospholipolysis of LDL produces high levels of lipid mediators, such as lysophosphatidylcholine (LPC) and free fatty acids (FFAs), which also modulate DC maturation. The major molecular species of LPC containing a palmitic or stearic acid esterified in the sn-1 position induce DC maturation, whereas the FFAs can positively or negatively modulate DC maturation depending on their nature. hGX-sPLA(2) added alone can also activate DC in vitro through the hydrolysis of the DC membrane phospholipids leading, however, to a different cytokine profile secretion pattern than the one observed with hGX-sPLA(2)-phospholipolysed LDL.
  
  
  CONCLUSIONS
  hGX-sPLA(2) secreted in inflamed tissues can contribute to local DC maturation, resulting in pro-Th1 cells, through the production of various lipid mediators from hydrolysis of either LDL and/or cell plasma membrane.
authors.affiliation: INSERM UMRS 937, Université Pierre et Marie Curie UPMC-Paris 6, Faculté de Médecine Pierre et Marie Curie, 91 Boulevard de l'Hôpital, Paris 75634 Cedex 13, France.
authors.forename: Rajai
authors.initials: R
authors.lastname: Atout
authors.forename: Sonia-Athina
authors.initials: SA
authors.lastname: Karabina
authors.forename: Sandra
authors.initials: S
authors.lastname: Dollet
authors.forename: Martine
authors.initials: M
authors.lastname: Carreras
authors.forename: Christine
authors.initials: C
authors.lastname: Payré
authors.forename: Patrice
authors.initials: P
authors.lastname: André
authors.forename: Gérard
authors.initials: G
authors.lastname: Lambeau
authors.forename: Vincent
authors.initials: V
authors.lastname: Lotteau
authors.forename: Ewa
authors.initials: E
authors.lastname: Ninio
authors.forename: Laure
authors.initials: L
authors.lastname: Perrin-Cocon
mesh_terms: D050197:Atherosclerosis / Q000201:enzymology* / Q000276:immunology; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D054509:Group X Phospholipases A2 / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D007371:Interferon-gamma / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000378:metabolism; D010641:Phenotype; D010713:Phosphatidylcholines / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology
chemical_list: D005230:Fatty Acids, Nonesterified; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines; D007371:Interferon-gamma; D054509:Group X Phospholipases A2; C516365:PLA2G10 protein, human