title: A matrix of cholesterol crystals, but not cholesterol alone, primes human monocytes/macrophages for excessive endotoxin-induced production of tumor necrosis factor-alpha. Role in atherosclerotic inflammation?
abstract: When exposed to small amounts of bacterial endotoxin, matrices of cholesterol crystals, but not cholesterol itself, primed human monocytes/macrophages to a highly augmented (>10-fold) production of inflammatory tumor necrosis factor-α. Priming also sensitized the cells, as 10- to 100-fold lower levels of endotoxin were needed for TNF-α production equivalent to that of unprimed cells. The pro-inflammatory effect was selective as endotoxin-induced production of other pro-inflammatory cytokines was unaffected while production of anti-inflammatory interleukin-10 was diminished. These findings suggest that cholesterol matrix formation may play a pathogenic role in atherosclerotic inflammation, and they indicate a mechanism by which bacteria and/or bacterial products may play a role in processes leading to arteriosclerosis.
authors: Institute for Inflammation Research (IIR), Rigshospitalet National University Hospital, Copenhagen 2100, Denmark.
authors: Klaus
authors: K
authors: Bendtzen
authors: Ole
authors: O
authors: Christensen
authors: Claus Henrik
authors: CH
authors: Nielsen
authors: Palle
authors: P
authors: Holmstrup
mesh_terms: D050197:Atherosclerosis / Q000473:pathology*; D002784:Cholesterol / Q000737:chemistry / Q000494:pharmacology*; D003460:Crystallization; D004731:Endotoxins / Q000633:toxicity*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008264:Macrophages / Q000473:pathology*; D009000:Monocytes / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol