title: Differentiation of human monocytes to monocyte-derived macrophages is associated with increased lipoprotein lipase-induced tumor necrosis factor-alpha expression and production: a process involving cell surface proteoglycans and protein kinase C.
abstract: The aim of the present study was to (1) evaluate the responsiveness of human mononuclear cells to lipoprotein lipase (LPL), as assessed by tumor necrosis factor-alpha (TNFalpha) production, during the process of differentiation of monocytes to macrophages, and (2) determine the mechanisms by which LPL exerts its effect on these cells. Treatment of human monocytes with purified endotoxin-free bovine LPL (1 microgram/mL) resulted in a 161+/-15% increase in TNFalpha production over control values (P<0.01). A further increase in TNFalpha production was observed after treatment of monocyte-derived macrophages (MDMs) with LPL (490+/-81% over control values, P<0.01). Increased TNFalpha mRNA expression and protein kinase C activity were also observed in LPL-treated human monocytes and MDMs. These LPL effects were abrogated by the specific protein kinase C inhibitor calphostin C (1 micromol/L). Although heparinase totally abolished LPL-induced TNFalpha production in human monocytes, this agent did not significantly inhibit LPL effect in human MDMs. In contrast, treatment of MDMs with chondroitinase suppressed LPL-induced TNFalpha production. Taken together, these data suggest that (1) differentiation of human monocytes to MDMs is associated with increased LPL-induced TNFalpha mRNA expression and production, (2) a protein kinase C-dependent pathway is involved in the induction of TNFalpha by LPL in these cells, and (3) LPL effect is mediated by cell surface proteoglycans. As MDMs secrete LPL in the vascular wall, we propose that LPL, by acting as an autocrine activator of MDM function, may contribute to the high level of TNFalpha found in the atheromatous lesion.
authors.affiliation: CHUM Research Center, Notre-Dame Campus, Department of Nutrition, University of Montreal, Montreal, Quebec, Canada.
authors.forename: J C
authors.initials: JC
authors.lastname: Mamputu
authors.forename: G
authors.initials: G
authors.lastname: Renier
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D002810:Chondroitinases and Chondroitin Lyases / Q000494:pharmacology; D005260:Female; D019763:Heparin Lyase / Q000494:pharmacology; D006801:Humans; D008071:Lipoprotein Lipase / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology*; D011509:Proteoglycans / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D011509:Proteoglycans; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D011493:Protein Kinase C; D008071:Lipoprotein Lipase; D002810:Chondroitinases and Chondroitin Lyases; D019763:Heparin Lyase