Postprandial human triglyceride-rich lipoproteins increase chemoattractant protein secretion in human macrophages

Abstract

This study tested the hypothesis that postprandial triglyceride-rich lipoproteins (ppTGRL) have inflammatory effects in primary human monocyte-derived macrophages (HMDM). ppTGRL were isolated from normolipidemic human volunteers, and the production of chemokines and of inflammatory prostaglandins and leukotrienes via the arachidonic acid cascade in HMDM was determined, and their effect on monocyte chemotaxis were assessed. In addition, the possible role of extracellular lipases in the inflammatory effects of ppTGRL was evaluated. ppTGRL were found to increase the secretion of chemoattractants, including monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein (MIP)-1α and -1β and IL-8, by HMDM and to have a stimulatory effect on monocyte chemotaxis. HMDM secretion of leukotrienes B4 (LTB4) and lipoxin A (LXA4), which are potent activators of monocyte migration, was also stimulated by ppTGRL. Inclusion of the lipoprotein lipase (LPL) inhibitor orlistat did not alter the effects of ppTGRL on chemokine production, and the expression of mRNA for LPL and other secreted lipases was unaffected by the lipoproteins. These findings support the hypothesis that ppTGRL induce the secretion of chemokines by macrophages which promote monocyte recruitment, and that extracellular lipolysis of the particles is not required for these effects and provide further evidence to indicate that the postprandial lipoproteins contribute to a pro-atherogenic pattern after a fat-rich meal.