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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:1405-1411.)
© 1999 American Heart Association, Inc.

Vascular Biology

Differentiation of Human Monocytes to Monocyte-Derived Macrophages Is Associated With Increased Lipoprotein Lipase–Induced Tumor Necrosis Factor- Expression and Production

A Process Involving Cell Surface Proteoglycans and Protein Kinase C

Jean-Claude Mamputu; Geneviève Renier

From the CHUM Research Center, Notre-Dame Campus, Department of Nutrition, University of Montreal, Montreal, Quebec, Canada.

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- (TNF) 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 µg/mL) resulted in a 161±15% increase in TNF production over control values (P<0.01). A further increase in TNF production was observed after treatment of monocyte-derived macrophages (MDMs) with LPL (490±81% over control values, P<0.01). Increased TNF 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 µmol/L). Although heparinase totally abolished LPL-induced TNF 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 TNF production. Taken together, these data suggest that (1) differentiation of human monocytes to MDMs is associated with increased LPL-induced TNF mRNA expression and production, (2) a protein kinase C–dependent pathway is involved in the induction of TNF 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 TNF found in the atheromatous lesion.

Key Words: lipoprotein lipase • tumor necrosis factor- • human mononuclear cells • proteoglycans • protein kinase C

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