title: OxLDL-IgG immune complexes induce expression and secretion of proatherogenic cytokines by cultured human mast cells.
abstract: OBJECTIVE
  Human atherosclerotic lesions contain mast cells and immunoglobulin G immune complexes containing oxidized low-density lipoproteins (oxLDL-IgG ICs). Here we studied whether such oxLDL-IgG ICs can activate human mast cells and induce them to express and secrete pro-inflammatory cytokines that are potentially capable of inducing and amplifying atherogenic processes.
  
  
  RESULTS
  Incubation of cultured human mast cells in the presence of oxLDL-IgG ICs led to a significant dose-dependent upregulation of the expression and secretion of tumor necrosis factor-alpha (TNF-a) and interleukin-8 (IL-8), and the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1). The secretory responses were dose-dependent and associated with moderate release of histamine and tryptase, which are preformed mast cell mediators contained in the cytoplasmic secretory granules of the cells. Also native LDL-IgG ICs induced similar pro-inflammatory cytokine response, suggesting that ICs per se are important for the IgG IC-induced mast cell activation.
  
  
  CONCLUSIONS
  Mast cells in atherosclerotic lesions which also contain oxLDL-IgG ICs may become activated by the ICs and secrete many pro-inflammatory cytokines. Our results suggest that intimal mast cells act as a cellular link between oxLDL-IgG ICs and the inflammatory response in atherosclerosis.
authors.affiliation: Wihuri Research Institute, Kalliolinnantie 4, FI-00140 Helsinki, Finland. jani.lappalainen@helsinki.fi
authors.forename: Jani
authors.initials: J
authors.lastname: Lappalainen
authors.forename: Ken A
authors.initials: KA
authors.lastname: Lindstedt
authors.forename: Riina
authors.initials: R
authors.lastname: Oksjoki
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
mesh_terms: D000936:Antigen-Antibody Complex / Q000378:metabolism*; D050197:Atherosclerosis / Q000276:immunology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006636:Histamine Release; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D053802:Tryptases / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000936:Antigen-Antibody Complex; C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D016209:Interleukin-8; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D053802:Tryptases